Transmission to humans usually occurs through contact with soil that contains infective S. stercoralis filariform larvae; such larvae develop from noninfective rhabdoid (rod-shaped) larvae in human feces. The filariform larvae penetrate the human skin, usually at the feet. They migrate by way of the lymphatic system to the bloodstream and lungs. Once they enter the pulmonary circulation, the filariform larvae break through the alveoli and migrate upward to the pharynx, where they are swallowed. They then lodge in the small intestine, where they deposit eggs that mature into noninfectious rhabdoid larvae. Next, the rhabdoid larvae migrate into the large intestine and are excreted in feces, starting the cycle again. The threadworm life cycle, from penetration of the skin by filariform larvae to the excretion of rhabdoid larvae, takes 17 days.

In autoinfection, rhabdoid larvae mature within the intestine to become infective filariform larvae.

If autoinfection is severe (disseminated strongyloidiasis), malnutrition from substantial fat and protein loss, anemia, and lesions resembling ulcerative colitis may result in secondary bacterial infection. Ulcerated intestinal mucosa may lead to perforation. Potentially fatal septicemia and massive invasion of organs can occur. These effects of autoinfection are most likely to develop in immunocompromised patients. (See Signs of disseminated strongyloidiasis.)