In Desert Rock, Arizona, Sheriff Jack Andrews asks country doctor Matt Hastings to inspect the body of Eric Jacobs, a scientist who has died in the desert outside the laboratory of nutrient biologist Dr. Gerald Deemer. Noting that Jacobs had contracted the rare glandular disease acromegalia, which, over the course of years, causes gigantism, Matt does not believe Deemer's claim that his partner's illness set in only days earlier. Back at his lab, Deemer continues experimenting with a growth-inducing serum, but just after he injects a tarantula, his other lab partner, Paul Lund, who is now deformed, breaks into the lab. Deemer realizes that Lund, like Jacob, has grown crazed after being injected with the serum, and to wreak revenge, Lund injects Deemer and breaks open the animal cages. As the tarantula escapes, a fire starts, destroying Lund and the other animals, and later, Deemer buries Lund in the back. The next day, Matt, still disturbed by the rapid onset of acromegalia in Jacobs, insists on an autoposy, but finds nothing. Matt prepares to visit Deemer's lab to investigate, and along the way bumps into pretty Stephanie "Steve" Clayton, a graduate student who has just arrived in town to serve as Deemer's new assistant. Matt informs her about Jacobs' mysterious death, and takes her to the laboratory, where Deemer, who wants only to create a food synthetic to solve world hunger, shrugs off Matt's questions. Later, the doctor explains to Steve the serum's solution, and the radioactive isotrope that triggers it, to Steve. Over the next few days, Steve marvels at the rapid growth of Deemer's baby rats, but also notes the growing deformities in his hands. One day, Matt drives Steve through the desert, and when they stop to admire the rock formations, the tarantula, now twenty stories tall but hidden behind the rock, causes an avalanche from which the couple barely escapes. When Steve then shows Matt the rats, Deemer, now more deformed and unnaturally enraged by the acromegalia, shouts at her for revealing their experiments. At the same time, Matt is stopped on the road by Jack, who asks him to accompany him to local rancher Andy Andersen's, whose cows have been eaten whole. There, they discover a pool of liquid on the paddock ground. Although Matt takes samples, he can promise no answers. That night, the tarantula returns and devours Andy, while simultaneously, Matt discovers that the liquid is insect venom and calls Deemer to ask about it. Steve answers and admits that she has grown scared of Deemer, who overhears and grabs her. Matt races to the lab, followed by the tarantula. Inside, Deemer has collapsed and Matt, realizing the doctor has acromegalia, revives him and puts him to bed. There, Deemer confesses what has happened to his other associates, stating that he wanted only to complete his experiments before he died. Hearing about the tarantula that escaped, Matt rushes to an entomologist, who confirms that the venom came from a huge spider that has become ferocious and deadly. Meanwhile, the tarantula, still growing, walks across the desert, destroying phone lines, and later grows fascinated by Steve's beauty and stares in through her bedroom window. Matt rounds up the local police and arrives at Deemer's in time to save Steve, but as they drive away, the tarantula tracks them. Along the road, two policemen try to shoot the monster down, but it repels the bullets, prompting Matt to suggest that they call in the Air Force to bomb it. While everyone huddles in the streets as the tarantula approaches menacingly, the pilots arrive and begin dropping napalm bombs. Just before the tarantula can destroy the town, the napalm finally hits it target, and the spider explodes into flames, leaving the town safe.