Both nifedipine and nitroglycerin are used to treat angina pectoris. The comparative effects of these agents on myocardial blood flow and contraction in the setting of flow-limiting coronary stenosis are poorly understood. Thus 24 open chest dogs underwent carotid to left anterior descending coronary arterial perfusion with coronary flow probe and perfusion pressure monitoring. Segment length was measured with ultrasonic crystals in the subendocardial ischemic and nonischemic zones. Myocardial blood flow was measured with radioactive microspheres. Partial coronary occlusion was performed to attain a diastolic perfusion pressure of 40 mm Hg. Twelve dogs received intravenous nifedipine, 3 micrograms/kg per min, and 12 received intravenous nitroglycerin to reduce aortic pressure by 20 mm Hg. Partial occlusion resulted in a slight but significant decrease in segment shortening in the ischemic zone. Neither nitroglycerin nor nifedipine affected shortening in the ischemic zone. After occlusion, blood flow decreased in the subendocardial ischemic zone but was unchanged in the subepicardium. Nifedipine increased subendocardial blood flow in the nonischemic zone and decreased it in the ischemic zone but caused no change in subepicardial flow in the ischemic zone. In contrast, nitroglycerin decreased subendocardial and subepicardial blood flow in both the ischemic and nonischemic zones. In the setting of coronary stenosis, different classes of vasodilators may have varying effects on myocardial blood flow, suggesting different sites and mechanisms of action. In addition, segment function may not always reflect changes in myocardial blood flow.