It is known that glutathione (GSH) has an immunological effect on several features of the immune system. The present study investigated the effects of GSH on interleukin-2 (IL-2) production from normal human peripheral blood lymphocytes (PBL). The results showed that both exogenous GSH and 2-mercaptoethanol (2-ME) significantly increased intracellular GSH levels after PBL were incubated with both agents. IL-2 production from PBL was markedly increased at the presence of exogenous GSH (0.5-8 mmol/l) or 2-ME (12.5-50 mumol/l) which corresponded to 1.57-2.82 nmol/10(6) cells and 1.41 - 1.80 nmol/10(6) cells of intracellular concentrations of GSH, respectively. However, IL-2 production seemed to reach a steady level when exogenous GSH concentrations in cell culture were between 2 and 8 mmol/l. The findings also showed that there was a positive correlation between the IL-2 concentrations and intracellular GSH levels. This study indicated that both exogenous GSH and 2-ME were able to elevate intracellular GSH levels and the increased intracellular GSH could increase IL-2 production in vitro. It is suggested that GSH may exert its effects on the immune system via the regulation of IL-2 synthesis.