We have previously documented the importance of tumor necrosis factor (TNF) alpha in the pathogenesis of nephrotoxic-serum nephritis in rats. In this study, we evaluated the possible relevance of the well-established cytocidal TNF activity to the mechanism of glomerular injury by assessing sensitivity of rat mesangial and epithelial cell populations to recombinant murine TNF alpha (rMuTNF). Radiolabelled confluent mesangial cell cultures that were incubated with rMuTNF released significantly more <sup>3</sup>H-thymidine than control monolayers (maximum specific release was 11.4 ± 4.9% at 1,000 pg/ml of rMuTNF). rMuTNF was, however, approximately 1,000-fold less cytolytic in mesangial cells than in the lymphotoxin-sensitive L929 cell line. Conversely, glomerular epithelial cells were not affected by exposure to rMuTNF under the same conditions. These results suggest that the cytolytic effect of TNF may contribute to glomerular injury in nephrotoxic-serum nephritis.