To determine whether released oxidants in endotoxemia contribute to the development of hepatocellular necrosis, we examined the effects of antioxidants and antioxidant enzymes on endotoxin hepatotoxicity in rats. In rats given endotoxin, focal and random hepatocellular coagulative necrotic areas with infiltration of polymorphonuclear leukocytes and mononuclear cells and an elevation of serum transaminase activities were found. The extent of hepatocellular necrosis and the level of serum transaminase activities were not significantly decreased by treatment with superoxide dismutase, catalase, alpha-tocopherol or allopurinol. These experimental data indicate that even if endotoxin is related to a release of oxidants, the oxidants do not appear to play an important role in the development of hepatocellular necrosis.