Special Agent Dana Scully is partnered with Special Agent Fox Mulder to validate his work on a special project called the X-Files. While he is a believer in the paranormal fueled by a lost memory of his sister's abduction, she is a scientist and prefers to look for rational, logical explanations. Their first case takes them to Oregon to investigate the unsolved murders of several High School classmates who "Spooky" Mulder believes have been experimented on by aliens.
Mulder and Scully head to Ellens Air Force Base to investigate the mysterious case of a military test pilot who disappeared after experiencing strange psychotic behavior. While on the case, Mulder meets a mysterious man dubbed "Deep Throat" who claims to have classified information about his investigations into the paranormal.
One of Scully's friends from the FBI academy, now working in the Violent Crimes Unit, asks her to assist him on a homicide investigation involving no clear point of entry. Mulder realizes that this is similar to a series of X-Files cases that have occurred every thirty years and joins in the investigation to stop the latest cycle.
When members of an Arctic research team mysteriously kill each other and themselves only days after drilling deeper into the ice than ever before, Mulder and Scully accompany a team of doctors and scientists to investigate. They discover an organism that infects living creatures and accelerates the hosts' feelings of anger and paranoia, and the agents' colleagues on the expedition begin to question their government knowledge.
Mulder puts the future of the X-Files in jeopardy when he heads to a UFO crash site being rapidly covered up by the military. He is arrested, and while in jail he meets Max Fenig, a UFO nut whose NICAP group has followed Mulder's work on the X-Files. When Mulder is released, Scully urges him to return to Washington to face his superiors and try to save his job, but Mulder finds out that Max is more than meets the eye and ignores Scully to try and save him instead.
When two fathers on opposite sides of the country are inexplicably murdered at the exact same time in the exact same way, Mulder and Scully are called in to investigate. When they discover that the two fathers' eight-year-old daughters are identical twins, they realize that something even stranger is going on.
When Deep Throat points out a news story about a fugitive who apparently drowned, Mulder and Scully cannot see what makes the case special but follow it up anyway. With Deep Throat's insistence, they discover evidence of a secret government project code-named Purity Control, which uses human test subjects and infects them with extraterrestrial DNA. However, the evidence and everyone who has seen it is quickly being eliminated.
With the X-Files closed, Scully has been assigned as an instructor at the FBI Academy while Mulder is doing menial surveillance work. After meeting with Senator Matheson, one of his supporters in regards to the X-Files, Mulder disobeys orders and heads to an abandoned SETI site in Puerto Rico which has inexplicably reactivated itself and could provide proof of contact with extra-terrestrial life.
While investigating the connection between the abduction of several teenagers and a rural religious cult, Mulder and Scully discover a secret test being performed on the children using the "Purity Control" alien DNA from 'The Erlenmeyer Flask' which leads Mulder to "the crew-cut man", Deep Throat's murderer.
The alien bounty hunter kidnaps Scully and wants to trade her for Mulder's sister, who is revealed to be a clone herself. After the trade goes badly and Mulder discovers the truth about Samantha, he tracks the bounty hunter to his ship buried in the arctic ice and demands the whereabouts of his real sister.
Mulder and Scully travel to Gibsonton, Florida, a town built and populated by circus and sideshow performers to investigate the death of Jerald Glazebrook, The Alligator Man. While searching for leads on the killer, the agents come across many bizarre characters including the local sheriff who was once known as Jim Jim, the Dog-Faced Boy.
A.D. Skinner and Scully are at a standoff when Mulder bursts in and discovers that Skinner has the digital tape. Reunited, Mulder and Scully travel to a secret vault inside a mine and find an elaborate filing system of medical records which reveals that Mulder's sister may not have been the first choice for abduction. Meanwhile, Skinner deals with the Cigarette-Smoking Man for their safety.
A French salvage ship searching for a lost WWII fighter plane unknowingly surfaces an alien which appears in the form of black oil and has the ability to jump hosts. Mulder heads to Hong Kong to investigate the salvage broker who sold the information to the French and he encounters Krycek, who has been selling information from the MJ documents. As Mulder prepares to take Krycek back to the US, the alien makes its way to Hong Kong and takes control of Krycek.
Jeremiah Smith and Mulder are on the run from the alien bounty hunter, and Smith takes Mulder to a small farm tended to by identical sets of children, and all the girls are clones of his sister when she was still a child. Mulder prepares to take Jeremiah and one of the clones to see his mother in the hospital, but the bounty hunter catches up with them. Meanwhile, the Syndicate suspects that they have a traitor in their midst and plan a trap which results in X being executed by the Cigarette-Smoking Man.
After an FBI raid on a doomsday cult called the "Temple of the Seven Stars", Mulder meets Melissa, a cultist who claims to have known him in a previous life during the American Civil War. Scully believes the woman is a delusional schizophrenic, but Mulder allows himself to be drawn into her fantasies.
Frohike pieces together and recites to Mulder and Scully what could be the possible life story of the Cigarette Smoking Man; from a young captain in the U.S. Army recruited to assassinate President Kennedy, to becoming the mysterious man in the shadows at the height of a global conspiracy. What measures will the Cigarette Smoking Man take to ensure that he remains a mystery forever?
A rock sample taken from Mars is intercepted at an airport and infects a security officer with the Black Cancer, while Mulder is given a tip about potentially dangerous paramilitary operations but is doubtful when the informant turns out to be Alex Krycek. Reluctantly, Mulder accepts Krycek's help and tracks the rock to Russia where he discovers an elaborate test being performed by Russian scientists.
After the body of a decapitated EMT disappears from the morgue and an identical man starts work at the same hospital, Mulder believes that the man has the ability to regrow parts of his body, including his head. The agents soon discover that Betts' body is riddled with cancer and he is able to live in that condition but needs to feed on cancerous tumors to keep up his strength.
While celebrating Scully's 33rd birthday, a strange woman informs Mulder that NICAP member Max Fenig (see Fallen Angel) has recently died in a plane crash. After a visit to the crash site and finding Max's body with radiation burns on it, Mulder suggests that the plane was intercepted by a UFO and is rapidly being covered up by the military.
Mulder is arrested for investigating the plane crash and interfering with a military operation, while Scully is caught in an attempted assassination of Corporal Frish which claims the life of Agent Pendrell. Scully bails Mulder out of prison, and they go to Max Fenig's trailer to find out why he was on the plane. Mulder finds evidence of alien technology and boards a plane with it, but the plane is intercepted mid-flight and it disappears. Mulder is again left with nothing.
A case involving a strange old man warning two scientists of events in the immediate future which come to pass (and the use of their experimental flash-freezing compound that does not exist yet) has Mulder believing that one of the scientists has come from the future to stop his own scientific breakthrough from becoming reality.
After a man sees a woman trapped inside a bowling alley pin setter, he goes for help and finds police standing next to a body of the same woman. Mulder and Scully join the investigation and follow up this lead which the police won't bother with, and they are led to a mentally challenged man who works at the bowling alley.
Scully helps Mulder fake his own death in order for him to go undetected through the Department of Defence and find out the answers to his new questions about the government hoax concerning the existence of extraterrestrial life. Meanwhile, at a joint FBI/DOD inquiry, Scully's attempt to drive out the Conspiracy's informant is halted as her cancer takes a bad turn.
The Cigarette-Smoking Man helps Mulder to obtain Scully's cure and also lets him see his real sister who doesn't turn out to be as happy to see Mulder as he would've liked. In return for this, the Cigarette-Smoking Man asks that Mulder quit the FBI and work for him in the Syndicate where he could have power and respect which Mulder turns down, deciding to stay on the side of justice. While Scully's cure appears to have worked, the Cigarette-Smoking Man faces his own enemies and disappears, presumed dead.
Set in 1989, the story of the founding of The Lone Gunmen is finally told as we see how a straight-laced federal employee, a sex mad AV expert, and a nerdy computer hacker meet Susanne Modeski, a strange woman with evidence of a government conspiracy. When their plan to expose the conspiracy fails and Susanne is captured by a group of men-in-black, led by none other than X, they soon become a paranoid group of government watchdogs.
On her Christmas vacation with her brother's family, Scully receives a mysterious phone call from a familiar voice who says, "She needs your help. Go to her." The phone call leads Scully to a murder case where the victim's 3-year-old adopted daughter bears an uncanny likeness to her sister, Melissa, at that age. The emotional roller coaster that follows has Scully believing that her sister had a baby during a period when she traveled the country and she tries to adopt the child, knowing that caring for the little girl would change her life.
After Mulder chases down and kills a young man who he believes to be a vampire, the agents return to DC aware of the mistake they just made. Faced with a lawsuit from the family of the man, they recount each of their sides to the story leading up to the event. In the extremely humorous stories that follow we see how Scully and Mulder both perceive each other.
Mulder and Scully meet Cassandra Spender, a woman who claims to be a multiple abductee and wants to deliver a positive message about the aliens. Mulder's new found disbelief in extraterrestrial activity is enhanced while Scully forms a special bond with the woman. A series of group attacks against abductees take place and the shadowy Syndicate believes that a rebel alien resistance is attempting to destroy all their work.
After the gathering at the abduction site where everyone is killed by the rebel bounty hunters, Cassandra Spender disappears and Mulder is blamed by her son, Jeffrey, who is an up-and-coming FBI agent. Meanwhile, the Syndicate is continuing their tests to create a vaccine for the Black Cancer and Marita Covarrubias becomes an unwilling test subject.
Mulder is less than thrilled when an Office of Professional Conduct board refuses to reassign him and Scully to The X-Files and even more so when he learns that Agent Spender and Agent Fowley have become their successors. When Gibson Praise reappears and comes to them for help, Mulder and Scully attempt to continue their quest undercover despite having fewer friends and less access and protection than ever before.
Mulder goes to the Bermuda Triangle when he learns that the Queen Anne, a British luxury liner which disappeared during WWII, has reappeared in the middle of the Sargasso Sea. Mulder's boat is wrecked and after floating in the water, he is hauled aboard the ship which has just been hijacked by the Nazis searching for the man who will build the atom bomb. Mulder tries to convince the crew that they have traveled into the future, but evidence further suggests that it is he who is back in the past.
While being detained near the famed "Dreamland" Area 51, a strange craft flies overhead and Mulder swaps bodies with an Area 51 "Man-in-Black". While the other agent has fun in Mulder's body, Mulder himself finds it difficult to fit into someone else's life, especially a shadowy one. Mulder contacts Scully about the body swap and tries to get her the flight data recorder from the UFO test flight, but his alter ego uses Mulder's FBI persona to have him arrested.
Mulder is thrown in jail at the Area 51 compound but is released when it is discovered that the flight data recorder he stole was a fake. Scully comes to her senses and realizes that the Mulder she sees isn't who he really is and heads back to Nevada to help the real Mulder. Meanwhile, the mechanism that caused the body swap is rapidly snapping back, undoing everything in its wake, and Mulder and his alter ego must race to put themselves back where they belong.
Mulder talks Scully into investigating a haunted house on Christmas Eve where several couples have met their fate on that very night. While there, they encounter endless tricks and traps set by a ghostly couple who originally made a lovers suicide pact in the house. The ghosts try to convince Mulder and Scully to kill each other.
After a scan of a couple's unborn child is found to have strange growths protruding from the head and back, the fetus is taken from inside the mother by a demon creature while she is asleep. Mulder heads to investigate after Agent Spender dismisses the claims, and discovers that the father is actually a demon who wants to have a normal child.
Mulder and Scully have 24 hours to save A.D. Skinner from being killed by a biologically engineered disease. The disease appears to be created by a shadowy government organization, but in order to save Skinner's life they must determine who wants him dead and why. With Skinner's condition worsening, Mulder seeks assistance from Senator Matheson, who he hopes can provide some answers and help him to find a cure.
Assistant Director Kersh tries to tear Scully and Mulder apart when he partners Scully with a New York agent investigating Alfred Fellig, a freelance police photographer who conveniently shows up to document the scene of a death as soon as it happens. While the young hotshot agent is convinced that Fellig is murdering the people, Scully has other (paranormal) theories.
While the Cigarette-Smoking Man recites to an unseen listener everything about the work of the Syndicate involving a global conspiracy in cooperation with an alien species, Cassandra Spender reappears and is pursued by the scientists who would rather kill her than keep her alive. Cassandra runs to Mulder's apartment and demands that he shoot her because she is the culmination of 50 years work - a living alien/human hybrid - and colonization will begin if the aliens find out about her.
The Cigarette-Smoking Man reveals all the government secrets from the past 50 years in order for his son, Jeffery Spender, to join him in his work. Mulder learns that the final stage of the conspiracy will soon begin with the hybridization of the Syndicate members, and he must stop it from happening. Agent Spender deceives his father and arranges for Mulder and Scully to be reassigned to the X-Files, which doesn't sit too well with the Cigarette-Smoking Man.
Arthur Dales summons Mulder and Scully to his holiday home in Florida where he is concerned over the disappearance of his neighbors. Despite the raging hurricane, Mulder and Scully head out to investigate and discover several strange deaths caused by an octopus-like sea creature that swam in through the overflowing sewer system.
Two scientists confer about each of their metal objects that were found in Africa and they theorize that the objects are pieces of a puzzle which could be undeniable proof that human, plant, and animal life did not originate on this planet. When one of the scientists is killed and the objects are stolen, the agents investigate and Mulder begins to experience severe neurological pain caused by the objects.
While Scully travels to Africa to piece together the meaning of the symbols on the spaceship beached on the Ivory Coast, Mulder is imprisoned by his own frenetic brain activity. He manages to get a message to Skinner who finds Kritschgau, and together they try to understand what is happening to Mulder before it is too late.
As the year 2000 draws closer, the agents are up against a man from the Millennium Group who believes that he can bring about the end of the world on the 31st of December if he resurrects four former members from the dead. To gain more insight into the group and its practices, Mulder and Scully enlist criminal profiler Frank Black to assist them in the investigation.
A young girl inexplicably disappears from her home, and Mulder requests the case even though it is a full FBI matter, not just an X-File. When Mulder takes some outrageous leaps to convince the girl's parents that she will be found, Scully fears that Mulder is becoming too personally involved with the case because of his sister's abduction.
After arresting the murderer of Amber-Lynn LaPierre and discovering a mass grave site containing the bodies of dozens of missing children, a man comes to Mulder and claims to have had visions of other victims who aren't buried at the site. Despite Scully's objections, he takes Mulder on a journey which reveals what truly happened to his sister.
The Lone Gunmen call Mulder and Scully to a virtual reality development lab where they learn that one of the program testers was killed inside the computer generated game environment by the digital image of a woman. Needing to get his yah-yah's, Mulder enters the game to fight the woman, but Scully must step in to save him.
Mulder and Scully watch a movie with themselves as characters and are thoroughly disgusted at how they and their case are portrayed on the big screen. They recount how 18 months earlier they were followed around by a Hollywood producer while investigating a case concerning The Lazarus Bowl - a mythical piece of pottery reputed to have inscribed on it the words that Jesus Christ spoke when he raised Lazarus from the dead.
Mulder and Scully return to the town of their first X-Files investigation where a UFO has crashed in the forest. The Cigarette-Smoking Man arranges for Krycek to be released from prison in order for him to make contact with the aliens and begin rebuilding the "Project", while Scully's health appears to be taking a turn.
Newly appointed Deputy Director Kersh organizes a manhunt for Mulder and assigns Agent John Doggett to head the team. Scully and Skinner go along with the investigation but are warned by Kersh that they will be fired if anything is said about aliens. Scully, along with the Lone Gunmen, surmise that the Bounty Hunter is trying to erase all evidence of abductions, and they realize that he may be going after Gibson Praise, who is now living at a school in Arizona. Agent Doggett comes to the same conclusion and his team race Scully and Skinner to the school where they find Mulder trying to kidnap Gibson.
When Teresa Hoese (the woman Scully and Mulder met the previous spring in Oregon just before Mulder was abducted) is found in a desert after enduring alien testing, Doggett alerts Scully that this could have something to do with Mulder and his whereabouts. Skinner joins them and they travel to the hospital where Teresa is clinging to life by a thread, and Scully realizes that this is exactly what's going on with Mulder.
Shortly after Mulder is buried, Billy Miles is found very dead, but he somehow comes back to life. Skinner and Scully put all their hopes into digging up Mulder and discovering that he too, is still alive. As Mulder lies in the hospital without indication that he is going to fully recover, Krycek comes to Skinner and offers him a vaccine to the virus that has infected Mulder, but the cost of the vaccine is that Skinner has to kill Scully's unborn child.
While Scully takes maternity leave, Doggett is partnered with a young agent who is fascinated with the X-Files and has followed Mulder and Scully's careers. She and Doggett investigate the death of an old man and the disappearance of his son, but when they disappear as well Mulder heads out to search for them.
Mulder and Doggett join forces to investigate the arson attack on a genetics lab where one of the doctors suspected of experimenting with alien impregnation is killed. They encounter Billy Miles, who has been changed into an alien replicant after his recent abduction and is attempting to erase evidence of the tests. When a woman helping Scully out at home is found to be a part of the conspiracy, the agents, along with Monica Reyes and Alex Krycek, know they must protect Scully and her baby from Billy Miles and get her out of the city.
During a stakeout of murderer Irwin Lukesh, Doggett sees Reyes attacked by Lukesh, but then we see Reyes and Doggett in her apartment, apparently both fine. Elsewhere at the same time, Doggett is shot and Lukesh identifies Reyes as the shooter. While Reyes is asked for her badge and gun by A.D. Follmer, and Doggett lies in hospital near death, the conflicting circumstances of the stakeout and Doggett's shooting do not add up and it becomes clear that Lukesh possesses the power to switch between parallel universes and alter the events in each.
Scully is approached by a couple who claim their baby has the same abilities as William and have information about the super soldier program; however, they will only talk to Mulder, believing him the only person who can make the connections and uncover the truth. Scully is forced into an awkward situation when she has to decide whether to put Mulder's life in more danger even though she desperately wants to see him.
Scully and Reyes join forces to try and find Doggett when he goes missing. Doggett has his own problems, having woken up in jail in Mexico suffering from amnesia. With no knowledge of who he is, Doggett is befriended by a local who soon has him working smuggling illegal immigrants across the border.
When pieces of the spaceship beached in Africa resurface, the conspiracy within the FBI attempts to hide the information from the X-Files, especially the one person for whom the pieces have a special significance - Scully. When Doggett and Reyes discover that Scully and her child have been put in great danger, they race to protect her and William from the evil forces pursuing him, and Scully is forced to take drastic measures to protect her child.
Scully is anxious to recover William from his kidnappers and takes matters into her own hands when the FBI's attempts to assist in the investigation are less than helpful. With the help of the Lone Gunmen, Scully discovers terrifying information about her child's captors, and is once again forced to confront the mystery regarding the sinister interest in her son.
Doggett catches someone in the X-files office trying to steal documents pertaining to Mulder's sister. The intruder is a severely scarred man who blames his disfigurement on Government conspirators. He claims the source of that information - and, in fact, the one who helped him gain entry - is Mulder. Although he refuses to divulge the missing agent's whereabouts, the mystery man has enough knowledge of the X-files and its history to lead Doggett to suspect that he just might be Mulder himself. Scully's fears for the safety of her son are elevated when he is injected with an unknown substance. With the mystery surrounding William becoming even darker, Scully must allow herself to send him away for his own safety.
When an FBI cadet with amazing profiling skills approaches Doggett, Reyes, and Scully with a lead on a suspect in a series of recent murders, he claims the same killer is responsible for the death of Doggett's son. The agents find themselves wondering if his knowledge of the deaths is because of his obsession with the cases he has studied at Quantico, or if he is in some way involved in the murders.
After not knowing Fox Mulder's whereabouts for the last year, A.D. Skinner and Agent Scully learn he's being held for the murder of a military man he couldn't possibly have killed: Knowle Rohrer, one of the government's secret super-soldiers. With Skinner acting as Mulder's defense, people who Mulder has dealt with during his last nine years as an FBI agent testify on his behalf. But the military tribunal isn't interested in the truth.
Fox Mulder and Dana Scully have been contacted by Tad O’Malley, a popular conspiracy theorist web-TV show host who believes he has uncovered a significant government conspiracy. With the assistance of FBI Asst. Dir. Walter Skinner, O’Malley seeks to enlist the help of former X-Files agents Mulder and Scully, who have since severed ties with the FBI. Through O’Malley they are introduced to Sveta, a possible alien abductee who shares shocking information with them that will challenge everything that Mulder has ever believed about the existence of aliens and the government’s role in covering them up.
The investigations that Mulder and Scully began with Tad O’Malley have awakened powerful enemies. A panic begins as people all over the country suddenly start falling ill, and Scully looks for a cure. Mulder confronts the man whom he believes to be behind it all, but another figure from their past may prove to be the key.