Marked increase in protein levels of Mn-superoxide dismutase (Mn-SOD) was found in TNF-resistant cell lines after treatment with Tumor Necrosis Factor (TNF). No such increase was observed in Cu,Zn-superoxide dismutase (Cu, Zn-SOD) protein in either TNF-resistant or sensitive cells. These results support the data that the Mn-SOD is one of the rescue proteins required for resistance to TNF cytotoxicity in these cell lines (Wong et al., Cell 58, 923-931, 1990). Mn-SOD was also responsive to TNF stimulation in KURAMOCHI, a human ovarian adenocarcinoma cell line. This may explain our previous result that Mn-SOD protein is highly expressed in epithelial ovarian cancer (Ishikawa et al. Cancer Res. 50, 2538-2542, 1990).