In the present work, the role of oxygen-derived free radicals in the pathogenesis of the gastric mucosal injury induced by cold-restraint stress was studied in rats. The results were as follows. (1) In rats pretreated with superoxide dismutase (SOD), a scavenger of superoxide anions, or with dimethyl sulfoxide and mannitol, scavengers of hydroxyl radicals, the gastric lesions induced by stress became much less extensive. (2) The mucosal content of malondialdehyde, a metabolic product of lipid peroxides, was significantly increased during stress. (3) Histochemical study revealed that the gastric mucosa abounded in xanthine oxidase (XO), the enzymic activity of which was increased during stress. In the rats pretreated with allopurinol, to inhibit XO activity, the extent of gastric mucosal lesions was decreased significantly. These suggested that oxygen free radicals might be one of the important factors in inducing gastric mucosal injury during stress and the increase of XO activity might be responsible for the production of the radicals.