Twenty patients undergoing open-heart valve replacement were divided randomly into two groups in this study; intermittent perfusion of cold crystalloid (St. Thomas Hospital solution) with hypothermic cardiopulmonary bypass (CPB) (hypothermic group) and continuous administration of warm blood cardioplegia with normothermic CPB (normothermic group) respectively. Tissue samples were taken from the right atrium before weaning from CPB and from the right appendage 30 minutes after removal of the cross-clamp. The results of pathological study in these two groups were as follows: the structural alterations were most severe during the ischemic period in the hypothermic group. Damages of the myocardial mitochondria examined with transmission electron microscope were found more severe in the hypothermic group than in the normothermic group, and in the reperfusion period than in the ischemic period. Loss of integrity of the mitochondrial membrane could be noted during reperfusion in the hypothermic group. The surface to volume ratios of mitochondria of each period of the two groups were calculated by computerizing the microphotographs of the myocardium. It was shown that the average of the surface to volume ratios was smallest in the reperfusion period in the normothermic group. It seemed that the volumes of the mitochondria were larger in the warm group than in the cold one. Probably the results were due to more severe damages of the mitochondrial membranes in the hypothermic group, which led to the release of the contents out of the mitochondria while in the normothermic group, the sodium-pump was disordered and it made the mitochondria swell. Pathologically, blood cardioplegic perfusion with the use of normothermic CPB is a feasible method for myocardial protection in open-heart surgery.