In the 1980s, Claire Redfield and her older brother Chris are children living at the Raccoon City Orphanage. Claire befriends Lisa Trevor, a disfigured girl who has been experimented on by Dr. William Birkin, an employee for the Umbrella Corporation, who takes children for his experimental research. Claire escapes the orphanage. In 1998, she returns to Raccoon City, hitchhiking in a semi-truck. The truck driver accidentally hits a woman on the road, who disappears. The driver's Dobermann licks the blood left behind, and over time becomes erratic. At a diner, rookie police officer Leon S. Kennedy notices that the diner's owner has blood coming out of her eyes. Claire warns Chris about Umbrella's experiments, revealing journalist Ben Bertolucci as her source. After Chris leaves, a child breaks into the house, running from his mother; both are erratic and bloody. Claire escapes. At the police station, the STARS Alpha team meets with Chief Brian Irons, who explains that the Bravo team went missing while investigating a death at the remote Spencer Mansion. The Alpha team, composed of Chris, Jill Valentine, Richard Aiken, Brad Vickers, and Albert Wesker, is sent to the mansion by helicopter to investigate. Unknown to his teammates, Wesker is an operative for an unidentified party, tasked with stealing William's virus. Inside, the team encounters zombies eating the bodies of the Bravo team. Brad gets bitten and crashes the helicopter. Richard is eaten; Chris and Jill flee into the secret passage Wesker unlocked. The truck driver, bitten by his dog, transforms into a zombie and crashes his truck in front of the police station. Chief Irons tries to drive out of the city but is fired on by Umbrella guards attempting to contain the outbreak. He returns to the station, where Claire and Leon encounter Bertolucci locked in a cell. Bertolucci is bitten by a zombie inmate and the station becomes overrun. Leon, Claire, and Irons escape to the Orphanage, looking for a secret Umbrella tunnel leading to the mansion. A Licker kills Irons and attacks Leon, but he is saved by Lisa. She recognizes Claire and gives them the keys to the secret passage. The pair discovers the secret lab where Umbrella was experimenting on children. Wesker encounters William and his family inside and has a shootout with them; he kills William's wife in self-defense. Jill shoots Wesker. Before apparently dying, Wesker tells her to escape via the underground train before the Umbrella Corporation destroys the city. William injects himself with the "G-Virus" and mutates. Chris, Jill, Claire, Leon, and William's daughter Sherry board the train but are derailed when Raccoon City is destroyed, allowing a monster version of William to reach them. Leon destroys the monster with a rocket launcher. As the Corporation states that there were zero civilian survivors in the aftermath of the destruction, the five survivors walk out of the train tunnel, leaving Raccoon City behind. In the mid-credits scene, Wesker awakens in a body bag, unable to see anything. A mysterious figure hands him sunglasses and introduces herself as Ada Wong.
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