The effects of an iron chelator on cellular injury induced by vascular stasis caused by hypothermia. Rewarming of a cooled rabbit leg was associated with the generation of oxygen-derived free radicals, shown to be instrumental for tissue injury occurring during rewarming. The present study used a compound that, by its ability to bind with free iron, can remove hydroxyl radical (OH.) from tissue. Deferoxamine reduced tissue injury during cooling and rewarming, as evidenced by its ability to decrease tissue release of lactic acid dehydrogenase and creatine kinase. Deferoxamine also reduced the formation of OH. and lipid peroxidation during the rewarming phase. This compound did not have any effect on the arterial blood flow pattern, which uniformly decreased during cooling and was restored during rewarming. The results of this study indicate the efficacy of deferoxamine in reducing cellular injury associated with cold and rewarming and further suggest a role for oxygen-derived free radicals in the pathophysiology of cold-rewarming injury. 