We studied the effect of nitroglycerin-induced decreases in mean arterial pressure (MAP) on myocardial salvage. Two hours after occlusion of the left anterior descending coronary artery, 65 conscious dogs were randomly allocated to receive 4 hr intravenous infusions of saline (group 1, 19 dogs), or nitroglycerin in doses to decrease MAP by 10% (group 2, 18 dogs), 25% (group 3, 14 dogs), and 50% (group 4, 14 dogs), respectively. At 7 days, 41 dogs were killed for measurement of infarct size; 24 dogs, given 7 to 10 micron radioactive microspheres for flow calculations, were killed 6 hr after occlusion. Boundaries of the occluded bed were defined by postmortem coronary arteriography. Infarct and occluded bed masses were measured by planimetry of weighed transverse sections of the left ventricle. Compared with saline infusions in group 1, nitroglycerin infusions produced sustained reductions (p less than .001) in mean left atrial pressure and MAP in all dogs, but heart rate was unchanged. The decreases in MAP achieved in groups 2, 3, and 4 were 10% (range, 5% to 19%), 23%, and 39%, respectively, with average levels of 96 (range, 83 to 113), 83, and 64 mm Hg, respectively. Despite similar masses of the occluded bed and left ventricle among the four groups, infarct size was significantly smaller (p less than .025) in group 2 compared with groups 1, 3, or 4, expressed both as percent of the left ventricle (6% vs 14% vs 13% vs 15%) and as percent of the occluded bed (13% vs 37% vs 34% vs 44%). Myocardial salvage (expressed as percent of the occluded bed) with nitroglycerin correlated inversely with the percent of decrease in MAP (r = -.77, p less than .001). Collateral blood flow increased (p less than .005) throughout the occluded bed in group 2 compared with group 1 but was unchanged in groups 3 and 4. In contrast, coronary vascular resistance decreased (p less than .025) in all nitroglycerin groups. These results suggest that perfusion pressure is an important determinant of myocardial salvage during nitroglycerin therapy. An increase in the dose of nitroglycerin to decrease MAP by more than 10%, and to levels below 96 mm Hg, might offset its potential for myocardial salvage in the conscious dog.