Dehydroepiandrosterone (DHEA), one of the predominant androgens secreted by the adrenal cortex, is a potential immunologic regulator. In this report, the effect of DHEA on interleukin-10 (IL-10) production was studied in vivo. Mice were injected s,c. with DHEA or DHEA-sulfate (DHEAS) ranging from 50 mu g to 500 mu g/g body weight. The serum was collected, and the spleen cells were isolated 48 h after treatment, Results indicate that treatment with DHEA or DHEAS significantly increases the serum level of IL-10, The spleen cells isolated from the DHEA-treated or DHEAS-treated mice also showed an increase in IL-10 secretion and mRNA expression after the cells were activated by concanavalin A (ConA). The maximal dose of DHEA for inducing IL-10 production was 250 mu g/g body weight. As IL-10 is a potent differentiation factor of B lymphocytes, the possible role of DHEA in regulation of immunoglobulin (Ig) production was studied in vivo, Results indicated a significant increase in both serum level of Ig (IgG, IgM, IgA) and Ig secretion by spleen cells after the mice were treated with DHEA or DHEAS, h lice injected with both DHEA (250 mu g/g body weight) and antl-IL-10 antibody (0.5 mg/g body weight) showed a significantly reduced DHEA-mediated increase in Ig production. Thus, DHEA might affect the function of B lymphocytes via stimulating IL-10 production.