Dehydroepiandrosterone (DHEA), the most abundantly secreted human adrenal steroid, has no known specific function. In spite of this fact there is an abundance of data associating DHEA with "health" in both man and experimental animals. Research in our laboratory has demonstrated evidence for an antagonistic interaction between DHEA and glucocorticoids (GC) in liver and brown adipose tissue. We hypothesized that DHEA also antagonized effects of GC on the immune system and that this "immune protective effect" might explain the diffuse positive effects of DHEA reported in the literature. Effects of GC on the immune system include involution of the thymus when given in animals in vivo and death of thymic lymphocytes in vivo with exposure to these steroids. We hypothesized that DHEA would block this GC mediated thymocyte destruction in vivo and in vitro. Pretreatment with DHEA for three days blocked approximately 50% of the thymic involution seen with dexamethasone. Results of in vitro experiments confirmed protective effects of DHEA in pretreated animals. (less than 50% of cell death in lymphocytes from pretreated mice compared with lymphocytes from control mice.) We conclude from these studies that DHEA protects against at least one GC anti-immune effect, thymic lymphocyte lysis.