To investigate the efficacy of human superoxide dismutase (h-SOD) in myocardial ischemia and reperfusion with difference of administration of h-SOD, twenty four dogs were subjected to 120min ischemia by the cross clamping of the ascending aorta, and followed by 60min reperfusion, The dogs were randomly assigned to three groups: group G, h-SOD (8mg/kg) was injected into the cardiopulmonary bypass (CPB) circuit 5min prior to reperfusion; group L, h-SOD (3mg/kg) was administered by bolus injection through the aortic root into the coronary artery 1min prior to reperfusion; group C, nothing was administered. The values of creatinine phosphate MB isozyme (CPK-MB) and a-hydroxydehydrogenase (HBD) in coronary effluent, and lipid peroxides (LPO) in coronary artery and sinus blood, were measured during CPB. Cardiac function was evaluated by cardiac index (C. I.) and LV max d_p/d_t, and it was expressed as a percent recovery of pre-CPB state. Myocardial water contents as myocardial edema were measured after CPB. Effluents of CPK-MB and HBD at 60min after reperfusion were less in group L than group G, C. Generations of LPO (A-Cs difference) were less at 5min after reperfusion in group G, L than group C and there were significant differences between group G, L and group C. The percent recovery of C. I. and LV max d_p/d_t at 60min after reperfusion was superior in group G, L than group C and there were significant difference between group G, L and group C. Myocardial water contents at 60min after reperfusion were less in group G, L than group C and there were significant difference between group G, L and group C. In the lipid peroxides generation, cardiac function and myocardial edema except effluents of cardiac enzymes, group G was as well as group L. These data suggest that the injection of h-SOD into the CPB circuit just before reperfusion is effective to prevent the reperfusion injury as well as the administration through the aortic root.