During experimental renal ischemia and reperfusion in rabbits, morphine as well as naloxone significantly inhibited the increased superoxide anion (O2-) generation by resting and opsonized zymosan-stimulated phagocytes in renal venous blood. Morphine with naloxone in combination inhibited O2- generation to a lesser extent than that observed when these drugs were used separately. Morphine and/or naloxone did not significantly affect erythrocyte superoxide dismutase (SOD-1), glutathione peroxidase (GPx) and catalase activities or malonyldialdehyde (MDA) concentrations in venous blood during renal ischemia. During reperfusion there was a tendency to a slight reduction of erythrocyte catalase activity in morphine-treated animals, and to slight diminutions of erythrocyte SOD-1 and GPx activities and erythrocyte MDA concentrations in rabbits treated with naloxone and morphine in combination. These results indicate that opioid receptor agonists and antagonists modify the response of the kidney to acute injury. These effects may have relevance to the pattern of oxidative stress seen in patients with acute ischemic renal failure.