Oxygen free radical injury during reperfusion of ischemically stored heart transplants may further impair the ability of the transplanted heart to reuse substrate for recovery. We compared the effects of oxygen free radical scavengers, superoxide dismutase and catalase, either alone or combined with glucose-insulin-potassium, in an improved model of the heterotopically transplanted rat heart. Group 1 hearts (n = 8) received no preservation before transplantation and were transplanted immediately. Hearts in four other groups (n = 8 for each group) underwent cold storage (4 degrees to 6 degrees C) for 3 1/2 hours before transplantation. Five minutes before reperfusion of the transplanted hearts, recipient rats received one of the following intravenous treatments: saline (group 2), glucose-insulin-potassium (group 3), superoxide dismutase/catalase (group 4), and superoxide dismutase/catalase plus glucose-insulin-potassium (group 5). Left ventricular end-diastolic pressure, rate of rise of left ventricular pressure, myocardial blood flow, coronary resistance, and tissue adenosine triphosphate content of the heart transplants were assessed during or at the end of 2 hours of reperfusion. Hearts treated with superoxide dismutase/catalase alone showed improvement of end-diastolic pressure and myocardial blood flow. The use of glucose-insulin-potassium alone did not facilitate the recovery of transplanted hearts. In contrast, the combined use of superoxide dismutase/catalase plus glucose-insulin-potassium resulted in a superior recovery of all functional and hemodynamic parameters. These results indicate that free radical scavengers in the presence of glucose-insulin-potassium significantly improve functional recovery in the setting of heart transplantation.