Feminine hands with huge, spider-like claws caress Doc Tucker. The chilling kiss ends with his lifeless body collapsing, and a disembodied voice asks the audience: > Have you ever been kissed by a girl like this?
American oil surveyor Frank and his Mexican assistant Pepe discover Grant Phillips and Doreen Culbertson wandering the Muerto Desert on the US–Mexico border, overcome by extreme dehydration and exposure. They bring the stranded pair to a field hospital run by the oil company, where Grant, still weak but alert, feverishly demands an expedition by oil truck to obliterate by fire the so‑called "super bugs" kept hidden in a secret underground laboratory on the isolated Zarpa Mesa. As Grant begins to recount his tale—from the beginning to Frank, Pepe, [Doc Tucker], and foreman Dan Mulcahey—a narrator overlays his account, nudging the focus toward Pepe and hinting at truths the Americans refuse to accept while the Mexicans already know.
A flashback, set a year earlier, introduces the enigmatic scientist Leland Masterson, who travels to Zarpa Mesa at the invitation of the reclusive Dr Aranya. Aranya’s work centers on growth hormones that can produce human‑sized tarantulas he can control telepathically and human women with the instincts and powers of spiders. His most famous creation, Tarantella, can regenerate severed limbs, and Aranya envisions a lineage of spider‑humans with superior intellect under his command. Masterson, however, denounces the project as evil and blasphemous. In retaliation, Tarantella injects him with a drug that renders him a simpleton, and after further experiments, Masterson is found wandering a desert and ends up in a lunatic asylum from which he eventually escapes.
The narrative resumes in a bustling border bar, where Leland Masterson—the scientist’s name now tied to the ominous past—finds himself alongside Jan van Croft and his fiancée Doreen, whose private aircraft has broken down. Masterson joins them, and Tarantella performs a hypnotic dance that captivates most patrons—except for George, a nurse from the asylum who has come to collect Masterson. Believing Tarantella’s danger, Masterson shoots her, then hardens his grip by taking Jan, Doreen, and George hostage. They are forced aboard Jan’s aircraft, joined by pilot Grant Phillips and servant Wu, who are added to the growing group of hostages despite the plane’s disrepair. Tarantella’s apparent death is only temporary, as she regenerates and slips away into the night.
Engine trouble and a failed compass set their flight off course, crash‑landing the group on Zarpa Mesa. [George] is killed exploring the harsh terrain, and Jan is wounded. As Grant and Doreen begin to lean on each other for comfort and courage, Wu’s treachery—sabotaging the airplane to aid Masterson—comes to light, and Wu is killed by the spider‑women. Jan’s guilt and fear take a toll, leaving him to suffer a mental breakdown before a giant spider ends his life. The survivors are quickly overwhelmed and captured, but Masterson’s mind is restored, and he is pressed into service to help neutralize Aranya’s experiments.
In a tense turn, Grant and Doreen restrain Aranya and Tarantella, enabling Masterson to devise an explosive plan for the laboratory. The trio manages to escape the facility as the laboratory and its horrifying experiments burn, with Masterson himself sacrificing much of his own safety in the blaze. Back at the field hospital, Grant’s account is met with skepticism by most, save for Pepe, who stands by the truth of what happened. The ending hints at a lingering presence—at least one of Aranya’s spider‑women endures, as Dolores Fuller’s character remains alive in the shadows of Zarpa Mesa, a reminder that the marvels and monstrosities of Aranya’s world might outlive their creators.