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Advances in genetic technology have allowed scientists to create sophisticated biologically-engineered humanoid beings called "replicants". Following a violent revolt that takes place "off world," replicants are declared illegal on Earth.
In Los Angeles, November 2019, Rick Deckard is called out of retirement when a fellow Blade Runner, Holden is shot administering a Voight-Kampff test to Leon, an escaped replicant. A reluctant Deckard is brought to his old boss Bryant, who informs him that the recent escape of Nexus-6 replicants is the worst yet. He orders Deckard to eliminate the four replicants, a process referred to as "retirement". Deckard agrees to help after Bryant makes thinly-veiled threats if Deckard is not a cop, then he is 'little people'.
Bryant briefs Deckard on the replicants: Roy Batty, the leader, is a "combat model"; Leon Kowalski is a nuclear fuel loader; Zhora is an assassin built for martial arts; and Pris is a "basic pleasure model". Bryant also explains that the Nexus-6 model has a four-year lifespan as a failsafe to prevent them from developing emotions and desire for independence. Deckard is then teamed with Gaff and sent to the Tyrell Corporation to ensure that the Voight-Kampff test works on Nexus-6 models. While there, Deckard discovers that Tyrell's young assistant Rachael is an experimental replicant who believes she is a human; Rachael's consciousness has been enhanced with implanted memories from Tyrell's niece, an accomplishment that Tyrell seems most pleased with.
Deckard and Gaff search Leon's apartment as Roy and Leon enter the eye manufactory of Chew; under interrogation, Chew directs them to J.F. Sebastian as their best chance of meeting Tyrell. Roy's plan to meet his maker is hampered by the urgency created by his limited lifespan; he is already exhibiting symptoms of impending death. Later, Rachael visits Deckard at his apartment to prove her humanity to him but leaves in tears after Deckard coldly tells her that her memories are implants. Meanwhile, Pris meets J.F. Sebastian and he invites her into his apartment in the Bradbury Building where he lives with his manufactured companions. In some versions of the film, Deckard is seen in his apartment daydreaming about a unicorn; he gets back to work and uses a computer scanner to find an image of Zhora in Leon's photos.
Deckard goes to Animoid Row to analyze a scale found in Leon's bathroom, which belonged to a snake made by Abdul Ben Hassan. After a rough interrogation, the snake dealer directs Deckard to a sleazy strip club owned by Taffey Lewis, who employs Zhora. After a struggle in Zhora's changing room and a chase through the crowded streets Deckard shoots and "retires" Zhora. Deckard meets with Bryant shortly after and is told to add Rachael to his list of retirements after she has disappeared from the Tyrell Corporation Headquarters. Deckard spots Rachael in the crowd and follows her but is grabbed and beaten nearly to death by Leon. Rachael saves Deckard's life by shooting Leon and they head back to his apartment where they have sex.
Back at Sebastian's apartment Roy arrives, kisses Pris deeply and tells her they are the only ones left. They employ Sebastian's help by explaining their plight in a subtly threatening manner. Roy discovers that Sebastian, though human, is suffering from a genetic disorder that accelerates his aging; he sympathizes with Sebastian because of their common fate. Under the pretext of Sebastian informing Tyrell of a move for a game of correspondence chess that Sebastian and Tyrell are playing, Roy and Sebastian enter Tyrell's penthouse. Roy demands an extension to his lifespan from his maker. Tyrell refuses to help because of limitations of nature that even he can't overcome. Roy then asks absolution of his sins, confessing that he has done "questionable things". Tyrell arrogantly dismisses this, praising Roy's advanced design and his amazing accomplishments. He tells Roy to "revel in his time". Roy kills Tyrell and Sebastian.
Deckard arrives at Sebastian's apartment and is ambushed by Pris. Deckard manages to grab his gun and retires Pris, just as Roy returns. Roy is horrified at her death. Angrily, Roy traps Deckard in the apartment, hunting him through the dilapidated Bradbury Building and eventually forcing him to the roof. The symptoms of Roy's limited lifespan worsen and his right hand begins to cramp, so he jabs a nail through it to regain control. As Deckard attempts to escape Roy, he leaps across to another building but falls short and ends up hanging from a rain-slicked beam. Roy easily vaults the same distance and is left standing above his struggling opponent. As Deckard loses his grip, Roy seizes his arm and hauls him onto the roof, saving Deckard. As Roy's life fades away, he calmly sits and delivers a soliloquy about the experiences of his life:
I've seen things you people wouldn't believe. Attack ships on fire off the shoulder of Orion. I watched C-beams glitter in the dark near the Tannhauser Gate. All those moments will be lost in time, like tears in rain... Time to die.
Roy dies peacefully. Deckard is left reflecting when Gaff, who arrives after the duel, calls from a distance, "It's too bad she won't live; but then again, who does?" A worried Deckard returns to his apartment and is relieved to find Rachael alive. As they leave, Deckard finds an origami unicorn, a calling card left by Gaff. Depending on the version, the film ends with Deckard and Rachael either leaving the apartment block to an uncertain future or driving through an idyllic pastoral landscape.