In 2004, the Umbrella Corporation's secret activities within Raccoon City have become a public affair. Following an investigation conducted by the U.S. government, several Umbrella officials are implicated and prosecuted. The government indefinitely suspends Umbrella's business, bankrupting the company.
Leon S. Kennedy was recruited by the U.S. Secret Service after they learned of his actions in Raccoon City. Leon is sent on a mission to rescue Ashley Graham, the President's daughter, who has been kidnapped by a mysterious cult. Leon travels to a rural village in Europe, where he encounters a horde of violent villagers who pledge their lives to Los Illuminados ("The Enlightened Ones" in Spanish), the cult that has kidnapped Ashley.
During the course of the mission, Leon is injected with a mind-controlling parasite known as Las Plagas. He is also reunited with Ada Wong, a woman from his past, and Jack Krauser, one of Leon's former comrades from his years of training, who was thought to be dead. He also meets Luis Sera, a former Los Illuminados researcher who aids Leon on his mission, but is later murdered by Osmund Saddler, the leader of the Los Illuminados cult. By examining Sera's notes, Leon discovers that Los Illuminados gained control of their subjects with Las Plagas. Their plan is to inject Ashley with a parasite, and then allow her to return to the U.S., where she can infect government officials.
After Saddler discovers that Leon has rescued Ashley, he commands his subjects to use any means to recover her. Meanwhile, after defeating the village chief, Bitores Mendez, Leon and Ashley take refuge inside the castle of castellan, Ramon Salazar. Ashley begins to cough up blood, indicating the slow maturation of the Plaga egg in her bloodstream. Distressed by this, she runs off. Leon eventually finds her, but she is later captured again. Leon then battles his way through the castle to find Salazar, only to learn that Ashley has been taken to a nearby island research facility. After numerous altercations with Saddler's forces, Leon is able to rescue Ashley, remove the Plagas from both of their bodies and defeat Saddler with Ada's assistance. Leon recovers a vial containing a Plagas sample from Saddler's body, but Ada forces him to give it to her at gunpoint. She then escapes from the complex in a helicopter, leaving Leon and Ashley to escape via her jet-ski.
