Dr. Neil Hamilton receives a call from his mentor Dr. Kate Travis [Jackie Burroughs] about a young boy named Bobby, whose deficient growth has been treated with Travis' experimental serum. Bobby has swiftly and unexpectedly grown larger than a full-grown adult and become violent. To find an antidote, Neil takes a sample of the serum back to his lab at a university science complex. There, animal-rights activists led by Mark Hales [Réal Andrews] and Neil's girlfriend Alex Reed [Lisa Schrage] protest the work of Prof. Edmund Delhurst [Colin Fox], who claims to study cancer but in fact subjects animals to experimentation seeking a cure for baldness.
Neil and his assistant Joshua inject the serum into some lab rats. That night, the activists (minus Alex) break into the complex to trash Delhurst's lab and accidentally release the now-giant rats, which kill Mark and escape into the campus' utility tunnels. Police Lieutenant Weizel [Michael Copeman] does not believe the surviving activists' statements despite Neil's corroboration about the serum, and Dean White [David B. Nichols] hires a pair of exterminators to handle what he believes are normal-sized rats.
The giant rats kill several people, including Louis, one of the exterminators; the surviving activists, Al [Stuart Hughes] and Angie [Karen Hines], escape. But the giant rats apparently kill whoever tried to hunt down the animals themselves. Delhurst's assistant, a janitor named Zeke, is attacked, but Jacques [Frank Moore], the surviving exterminator, despite taking several bites to his arms and face, appears and burns the rat. Later, a night watchman tries to escape some rats, though he is killed off-screen. Alex discovers the body of a workman (a man forced from his car and chased by rats) while two other men killed by the rats, whose bodies are still in the car, are discovered by the police. Although Lieutenant Weizel is convinced of the threat, Dean White remains skeptical and refuses to shut down the campus, due to the upcoming grand opening of the university's new sports complex. When Joshua falls victim to the rats, Neil attacks Dean White and is fired.
Delhurst steals the serum sample and tests it, first on Neil's pet rat Louise, then on a sample of cancer cells. He accidentally contaminates himself with treated cells and dies within minutes as his entire body develops massive tumors. Neil returns to the lab to retrieve the antidote he has created, testing it by destroying Delhurst's transformed corpse. Meanwhile, the rats attack the swim competition being held in the new sports complex, killing several people, including Dean White.
Neil uses the enlarged but still-docile Louise, who is in heat, to lure the giant (male) rats into the university courtyard, where Weizel and his men gun them down. Neil phones Dr. Travis to inform her of the antidote, but it is too late; Bobby, now psychotic and larger than ever, kills Travis while she is on the phone and escapes.