Leon, Claire, and Sherry prepare to leave the police station and heads to the sewer system in hopes of exiting the city premises.
Before they can proceed however, a creature with a pulsating, bulbous eye in its shoulder stand in their way. Wielding a pipe, it attacks them relentlessly, eventually tires itself before falling over a nearby railing. The bridge collapses from the strain of the fighting, and Leon falls down alongside the creature into the sewer. Upon recovering, he finds Ada again. She's trapped in a gun fight with another woman, who calls her a "thief".
Noticing Ada is making her move; leaving herself open to harm, Leon jumps between them and takes a bullet to the back in order to save Ada. The woman runs off, while Ada tends to Leon's wounds. He inquires about the altercation, and senses Ada won't be as forthcoming as he wants her to be. He insists she tell him more, but she reluctantly declines as she views the contents of a familiar looking pendant.
Sherry gets lost in the sewers system, and as Claire looks for her, she finds Leon limping not too far away. Leon explains what happened, and they continue looking for Sherry. Along the way they encounter Trenchy again and are forced to defeat him to progress. Multitudes of horrific creatures ranging from zombies, Web Spinners, Lurkers, and other creatures stand in their way but the two pushed on.
Suddenly, the woman who shot Leon appears, revealing herself to be Sherry's mother, Annette Birkin. Annette also turns out to be the wife of the creature with the bulbous shoulder-eyeball, now called G who was once none other than William Birkin. In a flashback, Annette tells Leon and Claire how the T-Virus Outbreak occurred. An Umbrella Special Forces unit led by HUNK tracked down Birkin with the intention of taking his G-Virus research and samples by force. Birkin resists, and they gun him down. HUNK retrieves the sample and departs, but Birkin decides to take his last G-Virus and inject it into himself in desperation. Now a rampaging G-Virus carrier, Birkin kills the entire unit, leaving HUNK as the only miraculous survivor.
Annette explains that any G-Virus carrier's instinct is solely to procreate, and Birkin's now primal instincts carried him to the police station, where he killed Ben, and implanted an embryo into Irons. Annette fears that he's after Sherry as he needs a host that are genetically compatible to him to procreate successfully. Upon realizing they both have the same goal of finding Sherry, they part ways and Leon and Claire move on ahead. They find Sherry, who panics and runs away. Just when things couldn't get any worse, a gargantuan crocodile infected with the T-Virus appears and attacks them. They're able to defeat it and reunite with Sherry. Their reunion is short-lived however, as things turned for the worse soon after.