Free radicals have been implicated in the damage caused by tissue ischemia and reperfusion. Canine kidneys were subjected to a 60-minute period of normothermic ischemia. One group of animals received intra-arterial superoxide dismutase (SOD, 17.6 mg/50 ml, 50,000 units) at the end of the ischemic period, whereas a second group received albumin (17.6 mg/50 ml). The kidneys treated with SOD demonstrated significantly less edema formation (1.0 +/- 0.3% wet weight vs. 1.8 +/- 0.2%, mean +/- SEM, p less than 0.05) and lower renovascular resistance (44.0 +/- 5.6 dynes-sec/cm5 vs. 64.0 +/- 12.0, p less than 0.05). The SOD group displayed greater preservation of both glomerular filtration rate (45.9 +/- 6.1% of baseline vs. 23.7 +/- 5.8%, p less than 0.05) and urine flow (1.3 +/- 0.4 ml/min vs. 0.3 +/- 0.1, p less than 0.05). We conclude that the free radical scavenger SOD provides significant protection of the kidney during ischemia and reperfusion.