The novel presents a day in the life of bounty hunter Rick Deckard, as he tracks down renegade androids who have assumed human identities in a post-apocalyptic world where animals are rare and the human population has largely migrated off-world.
The entire Northern California area is the territory of the district's senior bounty hunter Dave Holden. Deckard seldom works in it and does not consider himself to be either a peace officer or a full-time bounty hunter, but accepts the left-over cases that Holden either does not want or does not have time to pursue. On this day he learns that Holden has been hospitalized following an android attack during Holden's investigation into the recent escape of eight Nexus-6 androids, two of which were retired by Holden prior to the start of the novel, leaving Deckard to retire the remaining six. Deckard accepts the assignment in order to give his life meaning and combat the ennui of his existence and lack of social standing—a recent realization brought on by his wife's malaise and the social stigma of being too poor to own an organic animal pet.
The novel begins with Deckard feeling alienated from his wife, Iran, who misuses her mood organ device, intended to keep the population in even temper, by dialing the depression setting twice a month. Later Deckard has a conversation with his neighbor Bill Barbour as they tend to their domesticated animals. Deckard owns a malfunctioning synthetic black-faced Suffolk ewe being unable to afford an organic animal, while neighbor Barbour owns a real and pregnant Percheron mare. Discussing whether or not Barbour should sell the coming colt to Deckard, the latter realizes that owning a real animal would give meaning to his life.
Deckard travels by flying car to Rosen Industries in Seattle, Washington, to administer a bounty hunter "empathy test," a standard method for detection of androids posing as human in the form of a question and answer session, on the company's new Nexus-6 series. Deckard is introduced to and interviews a girl named Rachael, presented to him as the niece of Eldon Rosen, the head of the Rosen Association. Rachael eventually fails the test by hesitating in response to what should be normal human responses. The Rosens explain that Rachael is indeed human but lacks normal empathy due to being raised on a spaceship that was attempting to colonize Proxima before turning back.
Rachael attempts to bribe Deckard with the gift of a real owl, but during the conversation he verifies his finding that she was Nexus-6 and that Rosen Industries was just trying to discredit the empathy test. At first it appears that Rachael had memories implanted and is not aware she is not human; however, it's clear that this was a ruse and that she knows her origin and is being used by the corporation to protect other androids from bounty hunters through sexual favors.
Deckard ponders the meaning of humanity, morality and empathy following an attempt to retire an android opera singer. He is arrested and taken to a police station where he is accused of being an android before escaping with fellow bounty hunter Phil Resch after learning that the station was fake and staffed by androids. His moral quandary deepens after working briefly with Resch, whom Deckard first believes is an android but then learns is a particularly callous fellow human bounty hunter (Resch voluntarily took the VK test, preferring to find out if he himself is android or human).
Deckard's story is interwoven with that of J.R. Isidore (a surname Dick also used in Confessions of a Crap Artist), a "special" (i.e., genetically-damaged) driver for an animal repair shop who cannot qualify to leave Earth due to his "special" status. Isidore's low I.Q. is due to genetic damage induced by radioactive dust, and he lives alone in an empty apartment building with little outside contact. Pris Stratton, the same Nexus-6 model as Rachael Rosen, moves into the building and the lonely Isidore attempts to befriend her. Pris and her friends enlist Isidore to trap the bounty hunter chasing them down, and Deckard recruits Rachael to help him. However Rachael attempts to use her sexuality on Deckard to distract him from his work. Deckard and Rachael have sex. After Deckard confesses his love for Rachael, she reveals she has slept with multiple bounty hunters and, with the exception of Phil Resch, was able to dissuade them from retiring their Rachel-model targets via their empathy developed via her sexual favors. Deckard is tempted to retire Rachael but instead tells her to return to Rosen Industries.
As Buster Friendly unveils evidence that Mercerism is a fraud, and the androids discuss how Buster is actually an android, Deckard attacks them. Mercer appears and warns him of an ambush (incidently disproving Buster's thesis) so he succeeds in killing the androids. This causes Isidore to break down from the loss of his only friends, and earns Deckard a citation for a near-record number of kills in one day. He returns home and his wife reports having seen Rachael Rosen kill his new genuine animal he has bought with his bounty money that day, a pet goat, by pushing it off his building's roof.
He travels by flying car to a devastated area in Oregon to meditate and has an epiphany. He also finds a toad, thought to be extinct and considered to be Mercer's favorite animal. Deckard brings it home, where his wife discovers that the toad is in fact synthetic. While Deckard is not glad, he prefers to know the truth, whether the toad is real or artificial.