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Code 46 is a love story set in a Brave New World-type near-future where cities are heavily controlled and only accessible through checkpoints. People cannot travel unless they have “papelles,” a special travel permit issued by the totalitarianistic government, the “Sphinx”. Outside these cities, the desert has taken over and shanty towns are jammed with non-citizens - people without papelles forced to live primitive lives. William is a family man who works as a government investigator. When he is sent to Shanghai to solve a case of fake papelles, he meets a woman named Maria. Although he realizes she is behind the forgeries, he cannot help but fall completely in love with her. He hides her crime and they have a wild, passionate affair that can only last as long as his papelles: 24 hours. Back home, William is obessed with the memory of Maria. When the original investigation is inevitably re-opened a week later and William is sent back to finish the work he started, he tracks her down, only to discover she has been accused of a Code 46 violation and any further relationship is impossible.

Worn down and out of luck, aging publisher Will Randall (Jack Nicholson) is at the end of his rope when a younger co-worker snatches both his job and wife out from under his nose. But after being bit by a wolf, Will suddenly finds himself energized, more competitive than ever, and possessed with amazingly heightened senses. Meanwhile, the beautiful daughter of his shrewd boss begins to fall for him - without realizing that the man she’s begun to love is gradually turning into the creature by which he was bit.