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The novel begins with Jill running late for an emergency S.T.A.R.S. meeting in Raccoon City, Pennsylvania. The investigation of the recent cannibalistic murders was been put in their hands, but the S.T.A.R.S. Bravo Team was assigned with the mission and sent into the mountains. The police department has since lost contact with them. Jill wants to see the case closed as soon as possible, after the murders of local children, Becky and Priscilla McGee, of whom she befriended. As she gets ready to join the Alpha Team helicopter to search for the Bravos, a mysterious man named Trent appears in the locker room. He provides her with information about a mansion in the mountains - the "old Spencer place" - which contains a list of names of people connected with the building.

Arriving outside the mansion, the team find the wreckage of Bravo Team's helicopter. They are attacked by vicious dogs, with Joseph Frost being killed. The team's pilot, Brad Vickers abandons the team members in panic. Jill; Barry; Chris and Albert safely enter the mansion and split up to investigate.

Chris discovers Rebecca Chambers, the young Bravo Team medic, and partners up with her. Finding the remains of Bravo Team's Forest Speyer, Chris takes his friend's handgun and arms Rebecca. Meanwhile, Jill begins to suspect that something is wrong with Barry as be becomes increasingly absent, though is armed with a shotgun when Barry rescues her from a trap room with a collapsing ceiling. She is unaware that Captain Wesker is working to undermine his team's investigation, and has coerced Barry into helping him.

With everyone finding their way into the underground laboratory, Barry leads Jill into the Tyrant lab and sends her to Wesker - it is revealed that Wesker has had Barry's family taken hostage, and the takers have instructions to kill the family if they lose contact with the S.T.A.R.S. Captain. He eventually choses to betray his Captain and knocks him unconscious so the Alphas can escape. Escaping from the Tyrant lab and heading back to the surface, the four regain contact with Brad's an await his arrival. The Tyrant awakens and attacks the group, but Chris is able to destroy it with a rocket launcher. Back underground, Wesker regains consciousness and tries to activate the facility's self-destruct sequence. The Chimera B.O.W.s make and appearance and seemingly kill him.