Mutated spiders, mad geniuses, childlike mental patients, gold-digging blondes, and vengeful little people are only part of the madness in this legendary bit of oddball science fiction. Grant (Robert Knapp) and Doreen (Mary Hill) wander into a shack in the wastelands of Mexico's Muerto Desert, where the sunburned and dehydrated pair tell their tale to a surveyor for an American petroleum firm. Grant was working as a pilot for millionaire businessman Jan Van Croft (Nico Lek), who was to marry the much younger Doreen when engine trouble stranded them in a Mexican border town. Jan and Doreen were killing time in a roadhouse when they were joined by the eccentric Dr. Leland Masterson (Harmon Stevens), who had recently escaped from a mental hospital. Before Masterson's nurse, George (George Barrows), can lure his patient back to the hospital, Masterson pulls a gun and shoots entertainer Tarantella (Tandra Quinn) while she performs a wild dance routine; Masterson then takes Jan and Doreen hostage and demands that Grant fly them away. Further engine trouble strands the traveling party on a mesa, where they discover a handful of strange, tiny men and statuesque women. In time, we discover that Masterson knows the story behind the Mesa's unusual residents -- they're the products of a series of experiments by Dr. Aranya (Jackie Coogan), whose research into the pituitary glands of spiders has produced unusual results. The only screen credit for screenwriter and co-director Herbert Tevos (who helmed the project with Southern exploitation icon Ron Ormond), Mesa of Lost Women also features a memorably irritating guitar-and-piano score and a brief appearance by Dolores Fuller, best known for her work with one-time beau Edward D. Wood Jr.