May 20, 1998, the body of a young woman is discovered in the Marble River. Later, more murders occurred in the same fashion. The victims were apparently eaten. With this problem becoming out of hand, the S.T.A.R.S. were put on the investigation. On July 23, 1998, Bravo Team is assigned to the job. On their way to the murders sites, the team's helicopter malfunctions and is forced to land in the middle of Raccoon Forest.

The captain of Bravo Team, Enrico Marini, orders his subordinates to initiate a recognizance of the area. They discover an overturned MP vehicle. Among the remains of the vehicle, they find a file that explains what the vehicle was doing in the forest. It was transporting a prisoner named Billy Coen, an ex-marine. Billy had been court marshaled and sentenced to death. Enrico immediately gives orders to search for the criminal. The team's medic, Rebecca Chambers, starts to survey the area alone. She finds a train sitting motionless on it's tracks. She cautiously begins to approach it.

Rebecca notices that the passengers appear to be badly hurt. She walks down the aisle of the train, looking for any survivors. Soon she discovers that the passengers have turned into murderous zombies. While exploring the rest of the train, Rebecca comes in contact with Billy Coen. The fugitive points a gun at Rebecca but does not pull the trigger. Rebecca is confused and wonders if this is the dangerous criminal she is suppose to hunt down. Later on, They meet again and Coen tries to convince Rebecca about working together in order to help their chances of survival. She refuses. But when he saves her life and someone activates the train, Rebecca reconsiders the proposal and agrees to cooperate. Unknown to them, the train had been activated by two troopers under orders of Umbrella. The corporation wants to keep the outbreak of the T-Virus inside the train a secret. They program the train to run at top speed toward the next branch line and crash. Making it look like an accident.

What the Umbrella operatives can't figure out, is who or what caused the outbreak. The two troopers are then killed by the culprits of the spreading of the virus. They are in fact, mutated leeches. Hundreds of them have infested the train. And they seem to be following the orders of a strange cloaked man. This man controls the leeches with his singing voice. Rebecca and Billy begin their struggle to activate the train's brakes to try and slow it down and prevent it from derailing. They manage to activate the breaks. However, the train's speed is such that it loses it's grip on the rails when it hits a barricade inside a tunnel. It then lands on its side and slides into the tunnel before grinding to a halt.

Having survived the crash, the two protagonists find their way to a near by Umbrella Research Facility. Inside, they discover that the facility was in fact used to perform terrible experiments on animals. What's worse, most of the animals and creatures are still alive and show signs of suffering from a T-Virus infection. Rebecca and Billy look around the place, ignoring that they are being spied upon by two of Umbrella's most notable employees. Albert Wesker and William Birkin. They in turn become the targets of the cloaked man. The man seeks revenge on Umbrella and reveals that he is the one responsible for the outbreak in the Spencer Mansion and in the train.

Meanwhile, Rebecca and Billy search every corner of the facility, looking for clues that will open the way for them. The teamwork between them reinforces their friendship. Billy feels comfortable enough to confess to Rebecca the truth about the murders he is being charge with. At least what he remembers.

Their exploration leads them to nearby laboratories and interconnected underground facilities. The identity of the cloaked man also begins to unravel itself when pieces of his past turn up at various places. William Birkin and Albert Wesker also discover the truth about the man. Wesker does not allow the situation to affect his plans. He will bring another S.T.A.R.S. unit to the area and expose it to the creatures in a near by mansion. Birkin decides to destroy the place and everything in it. He plans to use a self-destruct device to blow the research facility, in the hopes it will also kill the cloaked man in the process.

That plan will also complicate the survival of Billy and Rebecca. Who already have their hands full dealing with the horrors within the facility and surrounding areas. And they will fall prey to the wrath of the man in the cloak...