Captain Thorne Sherman (James Best) and first mate Rook Griswold ("Judge" Henry Dupree) deliver supplies by boat to a group on a remote island. The group, consisting of scientist Marlowe Cragis (Baruch Lumet), his research assistant Radford Baines (McLendon), the scientist's daughter Ann (Ingrid Goude), her recent fiancé Jerry Farrel (Ken Curtis), and a servant Mario (Alfred DeSoto), welcome the captain and his first mate, but subtly resist the visitors staying overnight, even though a hurricane approaches. Thorne goes with the group to their compound. Griswold stays with the boat, to come ashore later.
The situation in the compound is less than safe. During evening cocktails, Thorne becomes aware of a life-threatening situation. Marlowe Cragis performs well-meaning research on serums and uses shrews as test animals. The doctor's purpose is to make humans half-size in order to reduce world hunger; smaller humans will eat less food on a planet with a limited food supply. Unfortunately, the doctor's experiments created mutant giant shrews that escaped and are reproducing outside the compound, growing larger by the day. The scientist and his staff barricade themselves inside their compound each evening.
Thorne and Ann begin to fall in love, causing jealousy in Jerry. Meanwhile, outside the compound, the giant shrews, which have a poisonous bite, are running out of smaller animals to eat. The shrews attack and kill Griswold. The giant shrews close in on the compound. One shrew breaks in through the window and hides in the basement. Mario and Thorne go down in the basement. Mario finds the shrew and shoots it, but it bites him. The shrew is then shot by Thorne and killed. The others arrive in the basement, but Mario dies. Radford discovers a highly toxic venom in the shrew's saliva, the result of poison bait he had placed in an attempt to kill the shrews. Another shrew breaks in and kills Radford. Before dying, Radford records the symptoms on his typewriter, right up to his death.
From outside the compound, the shrews begin to chew through the compound walls on the main floor. The shrews force the group (save for Jerry, who wants to stay) out of the compound to escape to Thorne's boat. The group makes impromptu armor out of oil drums, lashes the armor together, and duck-walks together to the beach. Jerry changes his mind about individualism, and chases after the others. The killer shrews chase and seemingly kill Jerry. The socially cooperative group (Thorne, Ann, and Marlowe) manage a successful armored walk to the shore and swim to the boat.
On the boat, Thorne and Ann share a kiss and the film ends.James Best as Captain Thorne Sherman
Ingrid Goude as Ann Cragis
Ken Curtis as Jerry Farrell
Gordon McLendon as Dr. Radford Baines
Baruch Lumet as Dr. Marlowe Cragis
"Judge" Henry Dupree as First Mate Rook Griswold
Alfred DeSoto as Mario
Principal photography took place outside of Dallas, Texas.
Special effects were provided by first-time director Kellogg, who served as the head of Twentieth Century-Fox's special effects department throughout most of the 1950s. Close-ups of the shrews were filmed using hand puppets, and for the wider shots, coonhounds were costumed as the shrews.
This low-budget feature was regarded as one of the most successful "regional films". Unlike other regional films, it received national and even foreign distribution.A new colorized version was released alongside The Giant Gila Monster as a double feature by Legend Films.
The TV show Mystery Science Theater 3000 riffed the film in an episode during the fourth season. The cast focused their gags on the main flaws of the film: the lack of conflict in the first hour of the film (which mostly focused on the living room of the island house and the characters talking to each other), the silly appearance of the shrews (dogs dressed to appear like them) and how most of the dialogue was hard to understand due to the accents of the characters. The MST3K version of the film was released by Rhino Home Video as part of the Collection Volume 7 box set.
A sequel, Return of the Killer Shrews, was produced in 2012, again starring Best as Thorne Sherman. Bruce Davison took the role of Jerry. The film also starred John Schneider and Rick Hurst, Best's co-stars in The Dukes of Hazzard. The length of time between the original film and the sequel release (over 54 years) is one of the longest between film sequels in history.