The effects of nitroglycerin on regional left ventricular performance, assessed by echocardiographic techniques, were investigated in anesthetized, open-chest dogs during acute myocardial ischemia. During transient occlusion of the left anterior descending coronary artery, there was end-diastolic thinning and marked reduction in systolic thickening in the central ischemic zone. Similar changes of lesser degree were noted in the border zone. The normal zone was unaffected. Infusion of nitroglycerin during ischemia in dosages of 2.5--50 microgram/kg/min reduced left ventricular end-diastolic pressure without changing the abnormalities of systolic wall thickening. Effects of bolus injections of 20 and 50 microgram/kg of nitroglycerin were similar, although this also lowered aortic pressure. In a subgroup of animals in which nitroglycerin infusion was unaccompanied by tachycardia, there was also no evidence that ischemic dysfunction was altered. We conclude that nitroglycerin does not improve regional myocardial performance in acutely ischemic canine myocardium. The decrease in preload is probably entirely due to the peripheral effects of the agent.