(Act Two is subtitled "In Vitro")
Prior lies on the floor of his bedroom, crying for Louis to wake up. Louis runs in, terrified; Prior is in terrible pain but refuses to go to the hospital. Louis runs out to call an ambulance, and while he is gone Prior has an accident that covers him in feces and blood. He faints, and Louis quietly despairs.
The same night, Joe comes home to find Harper sitting alone in the dark—she has been having drug-induced terrors. They talk about prayer, and he tells her that as a child he was fascinated with the story of Jacob wrestling with the angel. Harper admits that she is not sure whether she is going to have a baby, but adds that she thinks he should go to Washington without her. When he protests, she says she is going to leave him.
In the hospital, Louis talks to one of Prior's nurses, Emily, while Prior sleeps peacefully. She tries to console Louis, and to make conversation she asks Louis where the name Prior Walter came from. Louis tells her that Prior is descended from an old WASP family that traces its lineage back to the Norman Conquest. He reflects bitterly on his weakness and lack of devotion in the face of Prior's illness, and tells Emily he has to go for a walk in the park to think.
Joe and Roy sit in a bar late at night. Joe tells Roy about Harper's addiction, her difficult childhood and the strict standards of the Mormon Church. He says in spite of everything he loves Harper's troubled side best because of his own struggle to pass as a cheerful and upright person. Roy sympathizes but says that Joe belongs in Washington, with or without Harper. He tells Joe that he is prepared to be a father to him, to push him to achieve, in a way that might seem cold or unforgiving but which is really meant to toughen and protect him. Then Roy discloses that he is dying of "cancer"; Joe is stunned. As Joe and Roy talk, Louis cruises a man (played by the same actor who plays Prior) in the Ramble, a deserted region of Central Park where men meet in the night for sex. Louis asks the man to punish him, and they begin to have sex. When the condom breaks, Louis tells the man he doesn't care whether he infects him or not, but the man grows uncomfortable and leaves.
Prior is visited in his hospital room by Belize, a black ex-drag queen who is his former lover and a dear friend. Prior wants Louis by his side, but he is nowhere to be found. When he calms down, he tells Belize he has been hearing voices, but begs Belize not to tell the doctor since he also finds the voice sexually arousing and does not want to give it up. Belize tells Prior that no matter what, he will be by his side. As soon as Belize leaves, Prior resumes an interrupted conversation with the voice; it tells him that it is not a herald of death but a messenger sent to prepare him to perform a great work.