A study was undertaken to evaluate the effect of acute occlusion of a coronary artery during cardioplegic arrest on myocardial preservation and to elucidate the influence of reestablishment of flow versus continued occlusion during the phase of myocardial reperfusion. Coronary occlusion was simulated, and myocardial viability was determined by measuring tissue levels of adenosine triphosphate (ATP) and creatine phosphate (CP) in biopsies of the posterior left ventricular wall. Eighteen pigs were divided into three equal groups consisting of animals with (1) patent right coronary arteries during arrest and reperfusion, (2) occluded right coronary arteries during arrest and patent during reperfusion, and (3) occluded right coronary arteries during arrest and reperfusion. The results of ATP and CP measurements showed that while poorer protection was afforded during two-hour arrest when the coronary artery was occluded, the risk of damage was much greater during reperfusion. Failure to restore adequate blood flow by retention of occlusion caused a concurrent decrease in ATP and CP levels below prescribed limits of myocardial tolerance. When occlusion occurs in the clinical setting, impeding cardioplegia and reperfusion, the importance of revascularization is emphasized.