Interleukin (IL)-6 gene induction was studied in the murine cell line, L929r2, which is resistant to the cytotoxic action of tumor necrosis factor (TNF). Increasing concentrations of TNF slightly elevated the background levels of IL6 expression as compared to non-induced cells. Under conditions where the resistant cells are sensitive to TNF by combined TNF/IFN-gamma treatment, the IL6 levels were strongly induced. This induction could be further enhanced by the addition of lithium chloride, or reduced by inhibitors of cytotoxicity, such as dexamethasone. These results confirm our earlier conclusions regarding the close relationship between TNF-mediated IL6 gene expression and the pathway leading to cytotoxicity.