Dr. William Masters, a successful doctor of obstetrics and gynecology, begins his controversial study of human sexuality. Dr. Masters recruits Virginia Johnson to be his secretary, but she quickly advances to be a valuable associate.
The Provost shuts down the research when he hears about the couples study and Masters is forced to move it elsewhere. Dr. Masters blames Virginia and fires her, but keeps her on until he can find a replacement.
A woman pregnant with quadruplets comes to the hospital and Dr. Haas lobbies for the case. A female gynecologist joins the staff. Both Dr. Masters and his wife learn a secret and both get what they want.
Both Bill and Virginia have unexpected and unwelcome visitors at home. With the study back in the hospital, new participants are recruited. Ethan struggles to forget his feelings for Virginia.
William and Libby experience personal tragedy. Masters decides to pair Austin with a stranger. Virginia struggles with her parenting due to her long hours. Ethan's relationship with Vivian takes the next step, whether he likes it or not.
Bill and Libby vacation in Miami after losing the baby. Virginia attends a visiting doctor's speech and decides to investigate one of the claims on her own. Austin struggles with the reason for his non-performance in the study.
Virginia and William ramp up their participation in the study. Libby bypasses William and pressures Ethan to resume the treatments. Austin and Margaret ramp up their tryst leading to differing expectations. Ethan decides to commit to Vivian.
Virginia resumes pursuit of her undergraduate degree. Masters takes Virginia's suggestion and enlists the aid of a technician to construct a working camera to film the intimate workings during sexual intimacy.
Virginia and Dr. Masters move on to filming involuntary reactions during the study, with Jane as usual being the first subject. Ethan reveals information about his heritage that threatens their relationship.
A former study participant comes forward with news of her pregnancy. Ethan learns he has been effectively fired, but not for the reason he thought.
Masters and Libby compile study information for hospital-wide presentation; DePaul and Johnson travel to a medical convention; Virginia's ex returns finds Ethan playing father to his children.
Dr. Masters' big day is at hand after 12 months of studies. Without Virginia as a voice of moderation will Bill's pitch hit the mark? Margaret Scully is confronted with her husbands homosexuality and investigates what is involved with his 'treatment'. Dr. Austin Langham has a job offer from L.A and the climax to the episode sees Virginia Johnson reading the notes from Dr. William Masters presentation at home in the rain, to hear a knock at the door.