Exposure of oral tissue to components of smokeless tobacco (ST) increases susceptibility to oral cancer and periodontal disease. Altered T cell cytokine expression patterns due to ST components could affect the course of these oral diseases. To determine if ST components bring about changes in cytokine expression, T cells in whole splenic mononuclear cell populations (SPM) and enriched T cells, costimulated with anti-CD28 were exposed to 1:10(2) to 1:10(4) dilutions of ST extract and stimulated with anti-CD3, IL-2, IL-4, IFN-gamma and IL-10 were measured using enzyme immunoassays and RT-PCR. IFN-gamma production by enriched T cells costimulated with anti-CD28, was decreased at all concentration of ST while IL-10 production were decreased at 72 h in cultures with 1:10(2). IL-2 production was significantly increased upon exposure of T cells to 1:10(2) ST extract. ST did not significantly impact IL-4 production. Overall the data indicate that expression of key cytokines, IFN-gamma and IL-10, are consistently decreased upon exposure to ST while IL-2 is increased. Thus, exposure of T cells to physiological concentrations of ST can alter the T cell cytokine expression pattern as to potentially influence oral cancer and periodontal disease.