The aim of this study was to document the relationship between coronary pressure during reperfusion and myocardial recovery after hypothermic cardioplegia. Isolated canine hearts perfused by a support dog were subjected to 2 hours of cardioplegia at 20 degrees C. Three hearts were reperfused at each of the following pressures: 20, 40, 60, 80, 100, and 150 mm Hg. The reperfusion period lasted 30 minutes, with the pressure being raised gradually from zero to the test level over the first 2 minutes, then being held constant until the end of the period. The results showed that the normal dog heart after 2 hours of hypothermic cardioplegia is tolerant to a wide range of coronary pressures during reperfusion. Hearts reperfused at pressures between 40 and 100 mm Hg had similar values for coronary blood flow, coronary sinus oxygen saturation, myocardial oxygen consumption, lactate flux, contractility, and myocardial adenosine triphosphate content. If coronary reperfusion pressure was 20 mm Hg, [corrected] myocardial rewarming was delayed, myocardial oxygen consumption was decreased, and myocardial ischemia was manifested by marked lactate efflux, high myocardial lactate concentration, and depletion of adenosine triphosphate. If pressure was 150 mm Hg, coronary flow was excessive. To place these results in the context of coronary artery disease, we measured reperfusion pressure in coronary arteries distal to a stenosis in 10 patients studied at the time of coronary bypass grafting. In 13 arteries with major stenoses, distal mean coronary pressure averaged 31 mm Hg while the simultaneously measured mean aortic or radial artery pressure averaged 66 mm Hg. Thus the average gradient across the stenoses was 35 mm Hg (range 15 to 60 mm Hg). We concluded that in normal hearts without ischemic damage, reperfusion can be conducted satisfactorily at mean coronary pressures from 40 to 100 mm Hg. In setting the tolerable limits for reperfusion pressure in patients with severe coronary artery disease, one should make allowance for pressure gradients of up to 60 mm Hg between the aorta and the distal coronary artery.