The effect of Tumor Necrosis Factor (TNF) on VP16 or VM26 cytotoxicity was studied in a human glioblastoma cell line T98G, which expresses TNF-receptors. Although T98G cells did not produce TNF endogenously they were resistant to the cytolytic effect of TNF. T98G cells were also moderately sensitive to the action of VP16 or VM26. TNF given at 1000 U/ml was able to increase the cell drug-sensitivity significantly. This effect was due to an increase in the VP 16-induced cleavable-complexes by TNF. These findings suggest that TNF specifically sensitizes human glioma T98G cells to the effects of VP 16 of VM26.