The effect of the xanthine oxidase inhibitor, allopurinol, on myocardial ultrastructure after left circumflex coronary artery occlusion (40 min) with or without reperfusion (60 min) was examined in rabbits. Pretreatment of rabbits for 7 days with allopurinol (0.1% in the drinking water) resulted in a lower incidence of ventricular fibrillation in both ischemic and reperfusion phases. However, the number of Q waves, ST-segment elevation and premature ventricular contractions were similar in both groups of animals. Examination of hearts from allopurinol-treated animals revealed a distinct decrease in ultrastructural alterations following ischemia and reperfusion. Among the subcellular organelles studied, allopurinol had a preferential protective effect on the mitochondria both during the ischemic and reperfusion phases. In the allopurinol-treated animals, most mitochondria were intact and the cristae network preserved. Our study suggests that the preservation of mitochondrial structural and functional integrity by allopurinol may be an important determinant of its protective actions in myocardial ischemic/reperfusion injury.