The effectiveness of superoxide dismutase and allopurinol was evaluated in preventing reperfusion injury in Sprague-Dawley rats utilizing a limb replantation model after 6 hours of warm ischemia. Immediately prior to reperfusion of the replanted limb the animals received (intravenously) either a single bolus of superoxide dismutase (16,000 units/kg), a single bolus of allopurinol (45 mg/kg), both agents, or only control solutions. In the rats that received only control solutions, 30% of the limbs survived the ischemic insult. The group that received both superoxide dismutase and allopurinol had a 75% limb survival (P = 0.005). The animals that had only superoxide dismutase or allopurinol had 58% and 60% of the replanted limbs survive, respectively. This study suggests that the administration of superoxide dismutase and allopurinol may be helpful in the prevention of reperfusion injury in skeletal muscle in an acute injury setting (without pretreatment) and may thereby improve limb salvage after a significant ischemic period.