In the Resident Evil timeline, during the T-virus outbreak in Raccoon City, cockroaches were among the various types of creatures that succumbed to viral infection. These insects did not undergo any significant level of mutation after becoming infected, but like all T- infected life-forms they displayed heightened degrees of aggression. They become highly carnivorous and actively attack other creatures much larger than themselves. In fact, over the course of the outbreak, the cockroach population actually drove the city's rat population to extinction. Like humans infected with the T-virus, cockroaches also resort to cannibalism.

During the Raccoon City Destruction Incident, cockroaches normally remained confined to the city sewers and went largely unnoticed by the citizens. At least one unlucky citizen trying to escape the chaos aboveground attempted to escape town via the sewers, only to fall prey to a large swarm of these infected insects. Leon Kennedy and Claire Redfield also encountered infected cockroaches during their time in the city.

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