Transmural left ventricular biopsies were studied from 28 patients undergoing cardiopulmonary bypass with anoxic cardiac arrest. The myocardium was protected by topical cooling (20 degrees C) (Group 1, 15 patients) or by cardioplegia with St. Thomas' solution (Group 2, 13 patients). Biopsies were taken at the start of bypass and 3 to 5 minutes after unclamping of the aorta. Mean cross-clamp time was not significantly different between the groups (50 minutes for Group 1 and 53 minutes for Group 2; p greater than 0.05). The ultrastructural changes induced by ischemia and subsequent reperfusion were almost exclusively related to the mitochondria. The degree of mitochondrial damage was evaluated by a semiquantitative analysis based on mitochondrial fine structure. The frequency of severe postischemic mitochondrial damage was significantly higher in Group 1 (20.1% versus 2.7% in Group 2; p less than 0.05). Biochemical analysis of the biopsies indicates that the myocardial concentration of creatine phosphate decreases by about 50% after topical cooling (p less than 0.05). With St. Thomas cardioplegia, no significant change in the tissue level of this high-energy phosphate takes place. The results show evidence of the superiority of the St. Thomas cardioplegia to topical cooling alone.