Rick and Iran Deckard wake in their apartment. Iran refuses to use the Penfield mood organ to dial herself into happiness. Rick checks on his electric sheep on the roof. The world of post-nuclear San Francisco is established: Mercerism, kipple, the emigration imperative, and the social shame of owning fake animals.

John Isidore wakes in his nearly empty apartment building. He is a 'chickenhead' — radiation-damaged, legally prohibited from emigrating. He interacts with a wilted neighbor and watches Buster Friendly on his ancient television set. His loneliness is established as the emotional baseline of the novel.

Rick arrives at work and learns senior bounty hunter Dave Holden has been shot by one of six escaped Nexus-6 androids. Rick is assigned the remaining targets. He visits the Rosen Association to validate the Voigt-Kampff empathy test against real androids and a human control — and discovers the test's troubling limitations.

Rick tracks down Luba Luft, an android working as an opera singer, and is nearly arrested by a police officer who may himself be an android. He is taken to a police station he has never seen before — which his own department doesn't acknowledge exists.

Phil Resch shoots Garland without hesitation. Rick administers the Voigt-Kampff to Resch — who passes as human. Rick and Resch retire Luba Luft at an art gallery. Rick buys Luba a book of Munch prints before killing her. Resch shoots her anyway. Rick buys a real goat.

Rick calls Rachael Rosen and asks her to sleep with him, believing the Rosen Association's claim that it will blunt his ability to retire androids — and wanting to understand what empathy for an android feels like. The emotional and philosophical implications are laid bare before the act occurs.

Pris Stratton moves into Isidore's apartment building. She is one of the escaped androids, and Isidore knows it — or strongly suspects it — and doesn't care. He offers her friendship. She accepts it instrumentally, without warmth. The contrast between Isidore's genuine love for other beings and Pris's functional indifference is the novel's moral center.

Buster Friendly makes his long-promised announcement: Wilbur Mercer, the religious figure at the center of Mercerism, is a fraud. The footage of his endless climb was shot on a back lot; Mercer is revealed to be an elderly actor. The androids celebrate. Isidore is devastated — then realizes it doesn't matter.

Rick sleeps with Rachael. He finds he cannot feel differently about the remaining androids afterward — the Rosen Association's tactic has failed on him. He returns to his apartment to find his goat dead, thrown from the roof by Rachael. She has done this to other hunters. She confirms it without apology.

Rick arrives at Isidore's building and retires Pris, Roy Baty, and Irmgard Baty in rapid succession. Isidore watches, unable to prevent it, unable to understand why the law makes these deaths legal. Rick feels nothing — or tells himself he does.

Rick drives north into the empty wasteland beyond the city. He experiences what appears to be a direct encounter with Mercer — who confirms he is a fraud but insists Rick's experience of him was real. Rick finds a toad, believes it to be real, and drives home.

Rick returns home. Iran discovers the toad is electric — a hidden water dish reveals the maintenance panel. She calls a store to order artificial flies and a humidity box. Rick sleeps. The final image is Iran caring for the artificial toad with the same attention she would give a real one.