It is postulated that glutathione acting as a free oxygen radical scavenger may protect beta-cells from cytokine-mediated cytotoxicity in insulin-dependent diabetes. In this study the effect of glutathione in preventing the cytotoxic damage mediated by tumor necrosis factor-a in vitro towards a human beta-cell line (CM insulinoma) was investigated. CM cells were exposed in vitro to tumor necrosis factor-alpha, tumor necrosis factor-alpha plus glutathione or glutathione alone at different concentrations. The resulting cytotoxicity was measured using a colorimetric assay. Glutathione significantly reduced the cytotoxicity mediated by tumor necrosis factor-alpha in a dose-dependent fashion (P < 0.001). These results suggest a protective effect of glutathione on beta-cell cytotoxicity induced by tumor necrosis factor-alpha and encourage the use of glutathione in trials aimed at reducing the beta-cell damage occurring in insulin-dependent diabetes.