Oxygen free radicals have been implicated in postischemic tissue damage in a variety of experimental models including the island skin flap. Previous studies have demonstrated that supplementing animals with exogenous superoxide dismutase (SOD), a free radical scavenger, improves tissue survival in island flaps. No studies to our knowledge have attempted to inhibit endogenous SOD in a skin flap model. In this experiment 20 control rats demonstrated a 12.00% flap necrosis 7 days after a modified ventral island skin flap was raised. A second group of 20 rats were supplemented with exogenous SOD (50,000 U/kg 30 minutes preoperatively and 12 hours postoperatively) and demonstrated a statistically significant decreased flap necrosis of 5.28%. A third group of 20 rats received diethyldithiocarbamate (DDC, 0.5 gm/kg 12 hours preoperatively), an agent previously shown to inhibit SOD, and demonstrated a statistically significant increased flap necrosis of 19.77%. In a final group of 20 rats the effect of DDC was overcome by supplementation with exogenous SOD, obtaining a flap necrosis of 8.35%. Our results add further support to the importance of SOD and oxygen free radicals in postischemic tissue damage by demonstrating increased tissue necrosis with inhibition of endogenous SOD. This suggests that there is a baseline degree of SOD activity in ischemic areas working to preserve tissue. It appears that the copper-containing species of SOD found primarily in the cytoplasm plays a pivotal role in preservation of postischemic tissue.