In the near future, the world is divided into highly regulated cities and a marginalized underclass. Access to the cities is controlled through a special insurance policy, known as "papeles," which contains a person's identity and genetic information. William Geld, an insurance fraud investigator, is sent to Shanghai to investigate a forgery ring that creates fake papeles. He falls in love with Maria Gonzalez, the ringleader, and instead of reporting her, he names another employee as the forger. When Maria's client dies while using a fake papel, William is sent back to Shanghai to complete the investigation. He discovers that Maria has left the city, and when he tracks her down, she appears to have no memory of him or their time together. William finds himself drawn into a dangerous relationship with Maria, risking his professional career and marriage. They travel to Jebel Ali in the UAE, where they hide out in an old city and book a room. William reveals to Maria that she has been given a virus that induces an adrenaline rush in response to physical contact with him, and that she will be forced to report the further Code 46 violation to the authorities. They rent an old car and drive away to escape the authorities, but William crashes the car while avoiding pedestrians and they are both knocked unconscious. William wakes up in a hospital in Seattle with his wife and child by his side. He has no memory of Maria or their time together, as all memories have been replaced with memories of a successful investigation. Maria is exiled "outside," where she lives in the desert. Her memories of William are altered so she won't remember their love and can't betray anyone else.

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Some movies that have similar genres and were produced around the same time as Code 46 include The Prestige, Sunshine, Unbreakable, The Butterfly Effect, Children of Men, The X Files: I Want to Believe.

Code 46 was released in theaters on August 2, 2004.