The effects of in vitro treatment of cercariae, schistosomula, and adult worms of Schistosoma mansoni with 4 hypothalamic–pituitary–adrenal (HPA) axis hormones are described. Dehydroepiandrosterone (DHEA) had the strongest effect on viability. Cercariae were more susceptible to this hormone than schistosomula and adults. Mechanically transformed schistosomula showed 100% mortality (determined microscopically by progressive internal disorganization, development of lucent areas in the cytoplasm, and progressive loss of motility) after 48 hr, whereas physiologically induced schistosomula were more resistant, maintaining viability for up to 5 days of exposure. Males were considerably less sensitive than females to the lethal action of DHEA. When adult worms were paired, DHEA lethality was markedly reduced, with viability beginning to decrease only after 4 days in culture. Cortisol reduced the viability of each of the stages tested about equally. Corticotropin-releasing hormone (CRH) and adrenocorticotropin (ACTH) did not affect the viability of any stage. DHEA and cortisol significantly inhibited in vitro oviposition, whereas CRH and ACTH did not. DHEA and cortisol exerted their effects on schistosome viability and oviposition in a concentration-dependent manner. These results suggest possible new avenues for the control of schistosomiasis.