We studied the efficacy of resuscitation with antioxidants in an animal model of hemorrhagic shock. Male Sprague-Dawley rats were anesthetized, and 27 mL/kg of blood was withdrawn from the carotid artery over 2 minutes. The animals remained in hemorrhagic shock for 45 minutes, followed by 1 hour of resuscitation. Experimental groups were as follows: 1) 15,000 u/kg superoxide dismutase (SOD) in 54 mL/kg lactated Ringer (LR); 2) 175,000 u/kg catalase (CAT) in LR; 3) 15,000 u/kg SOD+175,000 u/kg CAT in LR; 4) allopurinol in LR; 5) deferoxamine bound to pentafraction (DFO), 27 mL/kg; 6) pentafraction alone; and 7) LR alone. Compared with resuscitation with LR alone, SOD and allopurinol improved survival over 72 hours, P < 0.05. Survival with SOD+CAT was not different from LR alone. Deferoxamine bound to pentafraction did not increase survival over that with pentafraction alone. CAT had increased mortality compared to LR, P < 0.01. The efficacy of both SOD and allopurinol in decreasing mortality suggests the importance of superoxide radicals after hemorrhagic shock and resuscitation. These and other antioxidants are potential therapeutic agents in the clinical setting of trauma and hemorrhagic shock.