On the heels of Masters’ proposal that they participate in the sexual response study, Johnson considers the best course of action to keep her job – only to find she no longer has one. The study has been forced out of the hospital and Masters believes Johnson is to blame. As Johnson fights to save her job and struggles to care for her kids, Masters moves his study to a brothel. But Masters soon discovers that the chaos of the cathouse is unmanageable without Johnson’s help.
Masters and Johnson continue their research in the brothel but skewed data confirms that Masters must get the study back into the hospital. At the hospital, Johnson is surprised to learn that a distinguished new doctor on the OB/GYN floor is a woman who has no interest in female solidarity. Meanwhile, Libby struggles to conceive and Dr. Ethan Haas gets the case of a lifetime – a woman pregnant with quadruplets.
With the study back in the hospital, Masters and Johnson recruit new participants on campus. But Johnson is shocked when her ex-husband George, who’s crashing on her couch, wants to sign up. Masters’ mother comes to visit, but her new take on life stirs up painful memories of his childhood. And Libby’s attempt at playing matchmaker with Virginia and Ethan doesn’t go as smoothly as she’d hoped.
When Masters and Johnson expand the study to include couples, they discover that the science of sex is easily complicated by the mystery of attraction. Johnson tries to connect with her son who prefers his dad. In anticipation of his baby’s impending arrival, Masters experiences anxiety about becoming a father. And Dr. Ethan Haas learns that dating the provost’s daughter could impact his medical career.
In the aftermath of the miscarriage, Libby and Masters travel to Miami for some much needed rest and relaxation, but Masters is drawn back into his work by a sexually adventurous couple next door. Alone in the hospital, Virginia enlists Jane in an effort to debunk Freud’s theory that one kind of female orgasm is better than another. And Langham finds an unlikely cure for his sexual dysfunction in Margaret Scully.
Masters and Johnson continue their sexual response study – now as participants – but Johnson fears their work may be interfering with Masters’ home life. Libby pressures Dr. Haas to resume her fertility treatments in secret. Meanwhile, Haas struggles to let go of feelings for Virginia as his relationship with Vivian deepens. And Margaret Scully, caught in her infidelity, confronts her husband on the mounting problems in their marriage.
Masters and Johnson decide that the best way to record their study findings is to film them, but to do so they have to enlist outside help. Johnson redoubles her efforts to get a college degree, only to find that Dr. DePaul’s Basic Anatomy class is a requirement. Meanwhile, Haas and Langham – both unsure in their relationships – convince each other of the merits of being a married man. And after Margaret catches him in a compromising position, Scully takes drastic steps to control his sexual impulses.
When Masters and Johnson decide to film external reactions in the study, they must convince Lester and Jane that their footage won’t cross the line into pornography. Haas and Vivian’s plans for a Presbyterian church wedding are sidetracked when Haas reveals he’s Jewish. Libby keeps her pregnancy a secret from Masters and instead encourages him to mend his relationship with his mother. But during late night visits to the hospital, Estabrooks observes Masters and Johnson’s intimate relationship.
The hospital takes part in a nationwide civil defense drill, and the heightened atmosphere escalates conflicts among the staff. A former study participant reveals she’s pregnant and wants to know the identity of the father. Masters and Johnson, their relationship strained after ending their study participation, butt heads on whether to maintain study confidentiality or take responsibility. Haas learns he’s been denied a future job at the hospital but wrongly assumes his breakup with Vivian is to blame. Margaret Scully seeks answers about her husband’s sexuality from an unlikely source.
With Johnson no longer on his team, Masters accepts Libby’s offer to help compile the study work for a hospital-wide presentation. But when Masters sees another doctor’s presentation put his colleagues to sleep, he becomes determined to grab their attention even if it means pushing through provoking, but incomplete, research. Dr. DePaul and Johnson travel to a medical convention and DePaul opens up on why her work on the Pap smear is so important. And Virginia’s ex-husband George returns to find Ethan Haas playing father to his children.
Masters’ work on human sexuality culminates with a hospital-wide presentation of his and Johnson’s research findings. But when Masters attempts to push the envelope with the external footage of the female orgasm, the doctors’ response to the film is not what he had hoped. Meanwhile, Haas entertains a job offer at UCLA Hospital and considers what a move would mean for his relationship with Virginia. Scully pursues electroshock treatment with the hope of curing his homosexuality but Margaret has second thoughts about the risks involved.
Masters delivers a baby with ambiguous genitalia and urges the parents not to surgically assign the child a sex out of fear or convenience. Meeting Virginia at a hotel for a secret rendezvous, the two of them divide their attention between sexual role-play and a championship boxing match, prompting Virginia to unearth the truth of Masters'' troubled childhood.
Langham observes Masters and Johnson exiting a hotel room and shares his suspicions with DePaul, who is forced to make plans for her work without Virginia's involvement. Meanwhile, Betty attempts to conceal her infertility from Gene; and Masters tries to bring Johnson aboard as his assistant only to be thwarted by the head of the hospital, who takes a prurient interest in Masters' study.
Masters continues to break new ground by continuing his study as the only white physician in a Negro hospital but at the cost of his gynecology practice. Libby is confronted by Coral's boyfriend, Robert, over her poor treatment of Coral, Betty reunites with her former lover, and Johnson struggles to right her relationship with DePaul - who is newly aware of Johnson's ongoing affair with Masters.
After Hendricks bans Masters from using black participants in his study, Masters contacts a journalist to promote his efforts, using the debunking of sexual stereotypes as the lure. Johnson is forced to accept DePaul's choice to end her chemotherapy treatments. Gene uncovers the truth about Betty and Helen's relationship. Libby fires Coral after discovering she lied about Robert.
In the wake of Masters' discovery that Johnson has continued to have romantic relationships with other men, he becomes impotent without her knowledge and cuts off their sexual work together. He tries to keep his new clinic solvent over the course of three years by borrowing against his house, offering medical services to the hotel - and finally accepting money from his mother.
Masters privately treats a couple for infertility, without revealing his relationship to them. Johnson realizes her work with Masters can be used to help people suffering from sexual dysfunction - but quickly gets in over her head when she attempts to treat Barbara Sanderson on her own. Libby is unnerved after witnessing a hate crime that is then whitewashed by the police.
Virginia continues to impersonate a patient's case history in order to glean advice from a psychiatrist. Betty and Masters' attempt to remedy Lester's impotence by hiring a prostitute rattles him even further. Libby gets the third degree when she offers her eyewitness testimony regarding the beaten man. And Barbara Sanders wrestles with an unsettling diagnosis that exposes a chain of secrets and causes Masters and Johnson to clash over their treatment strategy.
Masters learns of a rival study and calls in a public relations expert to help brand his work with Johnson. Virginia, having finally learned of Masters' sexual difficulties, is invigorated by the prospect of finding a cure. Determined to prove her worth to Robert, Libby canvases a tenement for a rent strike. Plus, Langham is stunned when Flo informs him that he has to have sex with her in order to keep his job. And Barbara and Lester connect over their shared sexual dysfunctions.
A television crew arrives at the clinic to document Masters and Johnson's work treating sexual dysfunction. Masters considers the publicity premature, and himself unsuitable as a television presence. Virginia deals with the fallout of having prioritized her work over her parenting when George argues to take their children on a trip with his new wife. Plus, Libby finds in Robert an appreciation for what she has to offer. And Langham realizes there's no way out of his sexual contract with Flo.
After watching an early cut of the documentary, Masters is disturbed by the portrayal of his work. Johnson's move to solidify her custody arrangement with George backfires. Finding justification in Masters' distraction, Libby continues her relationship with Robert. Langham discovers Flo's family's wealth and connections, causing him to re-evaluate his relationship with her. And after repeated testing of their protocol to cure impotence, Masters and Johnson feel they are ready to cure sexual dysfunction.