Cryptosporidiosis is a diarrheal disease in humans and other animals caused by the coccidian parasite, Cryptosporidium parvum. This study was undertaken to determine the effectiveness of dehydroepiandrosterone (DHEA) in reducing C. parvum infections in immunosuppressed adult C57BL/6N mice and to identify the immunomodulatory effects of DHEA that result in increased resistance to cryptosporidiosis. Dexamethasone-immunosuppressed mice were readily infected with C. parvum following orogastric intubation with 10(6) oocysts/mouse. DHEA treatment of these mice significantly reduced (P < 0.01) both fecal oocyst shedding and parasite colonization of the ilea. Immunosuppressed mice treated with DHEA had more splenic total T cells, CD4+ T cells, and CD8+ T cells than immunosuppressed mice that were not treated, but the differences were not always significant. Moreover, nonimmunosuppressed mice treated with DHEA had significantly more (P < 0.05) splenic total T cells, CD4+ T cells, and total B cells than nonimmunosuppressed mice that did not receive DHEA. Of particular interest was the significantly larger (P < 0.05) number of CD8+ T cells in immunosuppressed, C. parvum-infected, DHEA-treated mice compared with the same mice that were not treated. Up-regulation of the immune system by exogenous DHEA may be useful in the treatment and palliation of cryptosporidiosis.