Masters begins a new job at Memorial Hospital under Betty's extortion terms only to discover that his boss insists he leave Virginia behind in favor of a handpicked secretary. Meanwhile, Johnson is torn between pressing Masters to rehire her and staying by DePaul's side as her condition worsens.

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.

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.

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.