The age-related decline in immune function, which is thought to be responsible for the increased incidence with age of certain diseases, including cancer, has been attributed primarily to a loss of T-lymphocyte function. As free radical reactions may contribute to cellular deterioration and loss of cell function with age, we investigated the effect of adding an immunopotentiating antioxidant, 2-mercaptoethanol (2-ME), to the diet of BC3F1 mice in a longitudinal study. For the study, young mice were divided into two groups, one of which received the 2-ME-supplemented diet. Approximately every 3 months for 2.5 years, mice from each group were sacrificed and the spleen lymphocytes assessed for immune function (proliferative response to concanavalin A, phytohemagglutinin, and lipopolysaccharide and the humoral response to sheep red blood cells). The accumulation of fluorescent products indicative of free radical damage was measured in the spleen lymphocytes and the cytochrome P-450 content and activity assessed in the liver. The effect of the 2-ME-supplemented diet on the mean and maximum life span and tumor incidence was also determined. The results showed that the animals fed the 2-ME diet had an increased mean and maximum life span and a postponed onset and decreased incidence of tumors. In general the T-cell-dependent immune responses were higher in the 2-ME-fed mice compared to the controls when the animals were young. No difference was observed between the two groups during mid-life. The responses declined in both groups during the latter half of the life span, but the responses of the 2-ME-fed animals declined to a lesser extent. The accumulation of fluorescent products of lipid peroxidation damage was also delayed in the lymphocytes of the 2-ME-fed mice. Cytochrome P-450 content and activity in the liver was not different in the two groups. The results suggest that the antioxidant activity of 2-ME delayed the accumulation of free radical damage in spleen lymphocytes, which resulted in a delay in the decline of immune function and was associated with the decreased tumor incidence and increased life span.