Several factors including antigen concentration, the route of antigen administration, hormones and cytokines have shown to affect T cells to produce the distinct patterns of lymphokines which exert regulatory and effector functions of immune response. In this study, we asked whether administration of dehydroepiandrosterone (DHEA) to mice which were tolerized by high dose of antigen could modulate T cell functions to restore the suppressed cellular immune response and to produce the distinct lymphokines. An intravenous injection of high dose of sheep red blood cells induced suppression of delayed type hypersensitivity (DTH) and a single subcutaneous injection of the tolerant mice with DHEA restored the suppressed DTH response. Furthermore, in vitro treatment of spleen cells from tolerant mice with DHEA abolished the transfer of tolerance to naive recipients. Lymphocytes from the DHEA-treated tolerant mice produced more IFN-gamma and less IL-4 and IL-6 than the cells from tolerant animals without DHEA treatment. These findings indicate that DHEA could recover antigen-specific immune suppression by differentially affecting T cells to produce the distinct lymphokines.