We have investigated the possible protective effect of superoxide dismutase and allopurinol in a rat model of mild and severe hepatic necrosis produced by Corynebacterium parvum with or without endotoxin. Histology showed a sinusoidal mononuclear cell infiltrate with multiple granulomata but variable degrees of hepatic necrosis. In the severe hepatic injury model there was a reduction in mortality, associated with a decrease in histologic and biochemical evidence of hepatic necrosis, after treatment with superoxide dismutase. This protective effect was not demonstrated with partially heat-inactivated superoxide dismutase. In the mild hepatic injury model similar trends in reduction of serum levels of hepatic enzymes were observed after treatment with both superoxide dismutase and allopurinol. These results indicate that oxygen-derived free radicals may play an important role in the pathogenesis of hepatic injury in the rat.