A severely deformed man is found dead in the desert near Desert Rock, Arizona. Doctor Matt Hastings (John Agar) is called in by Sheriff Jack Andrews (Nestor Paiva) and wants to perform an autopsy. The sheriff sees no need and Doctor Gerald Deemer (Leo G. Carroll) agrees, since he is convinced that the man—biological research scientist Eric Jacobs—died of acromegaly, but Hastings knows that the disease takes years to kill and this case is only four days old.

In his research lab, Deemer keeps rabbits, rats, hamsters, and tarantulas of enormous size. His assistant, a student named Paul Lund (Eddie Parker) is deformed like Jacobs. He attacks Deemer, smashing the glass of the tarantula cage and setting fire to the lab. He stabs Deemer with the serum hypodermic and dies. Deemer puts out the fire and buries Lund in the desert.

A newcomer to the small town named Stephanie Clayton (Mara Corday) is called Steve. (The female leads in SF movies often have masculine nicknames.) She is on her way to a job at Deemer’s lab, but the only taxi in town is late, so she accepts a ride from Doctor Hastings. At the house, they run into local journalist Joe Burch (Ross Eliot), who is interested in Jacob’s death but not getting much information from Deemer, who says the fire was caused by an equipment malfunction, all the test animals died, and Lund took off. Steve’s job contract says she must live at the house.

Days later, the sheriff asks Doctor Hastings to help him examine picked-clean carcasses and pools of some white liquid. The tarantula is now the size of a tank. The next night, a rancher and two men in a pickup truck are killed. Hastings and Steve go to the lab as Deemer sleeps, and she shows him how radioactivity produces a super-nutrient which could provide unlimited food to humanity. As she shows him the test animals, Deemer appears and kicks Hastings out.

At a destroyed horse-ranch, Hastings finds pools of the white liquid. He flies samples to the Arizona Agricultural Institute in Phoenix. It is tarantula venom. Doctor Townshend (Raymond Bailey) assures him that tarantulas are generally not that dangerous for humans, but one big enough to produce so much venom might well be. He calls Steve, but Deemer grabs her and cuts the phone dead. Hastings flies back to Desert Rock and finds Deemer near death from acromegaly.

That night, the tarantula, big as a house, attacks the place. Deemer is killed by falling debris, but Steve escapes. Hastings picks her up in his car and they flee down the highway toward the town, pursued by the giant tarantula. The sheriff’s men discover that their guns are useless, and so is dynamite, though it destroys the road. As the town is evacuated, an Air Force fighter jet launches a napalm attack, incinerating the tarantula at the edge of town. The pilot is wearing goggles but we all recognize his voice as that of Clint Eastwood.

The film was directed by Jack Arnold and produced by William Alland, from a screenplay by Robert M. Fresco and Martin Berkeley, based largely on Fresco’s story for the 1955 Science Fiction Theater episode “No food for thought.” The special effects were quite advanced by 1955 standards. A live tarantula and giant mechanical legs were used and were more convincing than the ants in Them! As in Them!, the desert landscape, shot in Apple Valley, California, is used well. The same matte effects were used in The Incredible Shrinking Man, and in fact it was the same tarantula. The poster, of course, showed a woman in the spider’s jaws, though no-one but men were killed. It received positive reviews and was called one of the best giant insect films. It still has a Rotten Tomatoes review of 92%. This was Clint Eastwood’s second role after the one in Revenge of the Creature.