Cold water immersion restraint of the rat results in focal gastric mucosal erosions. The lesions are associated with powerful, prolonged-duration gastric contractions. Phasic gastric contractions may attenuate gastric mucosal blood flow, resulting in ischemia followed by reperfusion. Therefore, the conditions of cold-water-immersion restraint might lead to mucosal injury by an oxyradical-mediated mechanism. To test this hypothesis, we studied the effect of oxyradical inhibition on cold water immersion restraint-induced lesions. In separate groups of rats subjected to cold water immersion restraint (6-10 animals per group), oxyradical inhibition was achieved by chronic feeding of a sodium tungstate diet, oral administration of allopurinol, or intraperitoneal administration of dimethylsulfoxide. None of these regimens significantly attenuated the number of lesions per stomach, the total lesion area, or the percent of corpus mucosa containing lesions. We conclude that oxyradicals do not play a role in the pathogenesis of cold water immersion restraint-induced lesions.