The role of oxygen-derived free radicals and lipid peroxidation in the pathogenesis of acute gastric mucosal erosion was investigated in rat models produced by burn shock stress, by treatment with regional hyperthermia, platelet activating factor, and compound 48/80, and by ischemia-reperfusion. In all experimental models, the increase in the gastric erosions and in TBA reactants in the gastric mucosa were significantly inhibited by the treatment with superoxide dismutase (SOD) and/or catalase. Pretreatment with allopurinol, a competitive inhibitor of xanthine oxidase, prevented considerably the gastric injury (a) induced by burn shock, (b) produced by treatment with compound 48/80, and (c) caused by ischemia-reperfusion. By the treatment with anti-rat neutrophil antibody, the gastric mucosal injuries induced by regional hyperthermia, platelet activating factor, and compound 48/80 were significantly inhibited; however, burn shock and ischemia-reperfusion injuries were not inhibited. These results suggest that oxygen-free radical and lipid peroxidation contribute to the formation of gastric mucosal lesions, and that the sources of oxygen radicals seem to be different among these experimental models.