Recent reports have demonstrated that the HIV-1 transactivator protein,tat, induces apoptosis in T-lymphocyte cell lines, as well as in peripheral blood mononuclear cells, and stimulates a cascade of events resulting in up-regulation of the potent immunosuppressive cytokine, transforming growth factor-β (TGF-β). In this study we evaluated the ability of TGF-β to mediatetat induced apoptosis in T-lymphocyte cell lines. T-cells treated exogenously with either TGF-β1 or a combination of tat and pan-specific TGF-β neutralizing antibodies showed little change in the amount of apoptosis. When treated with pan-specific TGF-β neutralizing antibodies, Jurkat cells that stably expresstat protein (Jurkat-tat) showed only a modest decrease in apoptosis, while CEM-TART cells (CEM T-cells expressing both HIV-1tat andrev) demonstrated little change in the amount of apoptosis. In conclusion, we have demonstrated that TGF-β does not play a significant role in mediatingtat induced T-cell apoptosis.