One day while riding across his Arizona cattle ranch, Cole Hillman is forced to shoot his horse after it stumbles on a rabbit hole and breaks its leg. Cole despairs the swarms of rabbits that have taken over his grazing land, and desperate for a safe solution, discusses the problem with old friend Elgin Clark, an administrator at the local university. Cole explains that the rabbit explosion came about after other ranchers all but wiped out the coyote population, thus destroying the rabbits’ natural predator. When Cole declares his desire to control the rabbits without resorting to chemical means, which he worries will adversely affect the land’s ecological balance, Elgin advises him to see Roy and Gerry Bennett, married zoologists newly hired at the university. Elgin talks first with the Bennetts and details Cole’s situation. After Elgin explains that Cole is an important backer of the school, the Bennetts agree to do what they can to help him. The Bennetts and Cole discuss possible strategies for diminishing the rabbit population, including hormonal treatments to curb their reproduction. Aware that the other ranchers are planning to poison the rabbits with cyanide soon, the Bennetts begin work immediately, using rabbits supplied by Cole. They quickly realize, however, that their strategies will take too long to perfect and turn instead to a new serum developed by Professor Dirkson for the Public Health Department. According to Dirkson, the serum is designed to create genetic mutations that will lead to life-threatening hereditary problems for the rabbits. Knowing the serum is untested, the Bennetts round up fifty rabbits to create both test and control groups and give a rabbit named Romeo the first injection. Afterward, their young daughter Amanda, who loves Romeo, secretly switches him with another rabbit, and unaware of the switch, the Bennetts allow her to adopt Romeo. Later, Amanda and Cole’s young son Jackie are playing with Romeo at the ranch when the rabbit escapes. At the same time, the Bennetts observe that some of the injected rabbits in the lab have grown disproportionately large. Soon after, the Bennetts and Cole notice huge animal tracks at a watering hole on the Hillman grazing land and begin to worry. Jackie, meanwhile, takes Amanda to visit an old prospector named Captain Billy, who has a nearby cabin next to an abandoned mine. Billy is nowhere to be seen, however, and while Jackie searches the cabin and spots huge animal footprints, Amanda enters the mine. In the semi-darkness, Amanda comes upon Billy as he is being attacked by an enormous rabbit, and shrieks in horror. Jackie rushes in to save Amanda, who becomes mute with terror. Later, he admits to the Bennetts that he did not really see anything in the mine. That night, a truck driver is forced to stop on the road that runs by the Hillman ranch and is killed by a group of giant, hungry rabbits. After Billy’s and the trucker’s bodies are discovered by the police the next day, Sheriff Cody orders the trucker’s body sent to forensic scientist Dr. Leopold. Leopold’s examination reveals that the trucker was attacked by a large, unidentifiable creature with a bite like a sabertooth tiger. Presented with Leopold’s findings, Dirkson concludes that one of the experiment’s rabbits must have escaped and introduced a defective gene into the general rabbit population. After Elgin, worried about adverse publicity for the university, suggests that the rabbits be killed by any means necessary, he, the Bennetts, Cole and Cole’s ranchhands, Jud and Frank, undertake to locate the animals on Cole’s land. Using rifles, dynamite and poisonous gas, they trap and kill many of the rabbits, but many others flee the ranch in a thundering stampede. While attempting to photograph the rabbits in the mine, Cole and Roy barely escape with their lives, and Gerry has to fire a quick rifle shot to save Jud from a rabbit ambush. Later, after residents of Gallanos, the nearest town, are slain by the rabbits, the National Guard arrives and evacuates Woodale, the next town on the creatures’ path. Unknown to Roy, Gerry and Amanda, who are driving their camper toward Woodale, have become stuck in a ditch just outside the town. That night, Cole comes up with a plan to herd all the rabbits toward a train switching station and electrocute them. Short on men, the National Guard recruits patrons at a drive-in movie theater to help trap the animals. Gerry and Amanda, meanwhile, are still mired in the ditch when they are encircled by a horde of giant rabbits. Using road flares, Gerry does her best to keep the rabbits at bay, while a few miles away, Roy commandeers a helicopter to find his family. At the switching station, Cole is frantically wiring the train tracks with high-voltage electricity, while the Guard and the townspeople line up their vehicles to form a barrier. After Roy locates and rescues Gerry and Amanda in the helicopter, the Guard opens fire on the approaching rabbits, forcing them onto the tracks. The switch then is thrown, and the rabbits are electrocuted. Months later, Cole informs Roy that, with the return of the coyotes, the rabbit population is back to normal, and the natural balance of the land has been happily restored.