The effects of nicorandil and nifedipine on ischemia--reperfusion-induced myocardial infarct size following a 2-h occlusion and 30-min reperfusion period of the left anterior descending coronary artery (LAD) were compared in anesthetized dogs. Myocardial blood flow was measured using the radioactive microsphere technique, and infarct size was determined using triphenyl tetrazolium chloride histochemical stain. Vehicle, nicorandil (100-micrograms/kg bolus followed by 25 micrograms/kg/min), or nifedipine (10-micrograms/kg bolus followed by 1 microgram/kg/min) was administered intravenously 10 min after LAD occlusion and infused throughout the occlusion and reperfusion periods. Nicorandil and nifedipine reduced mean arterial blood pressure similarly (15 mm Hg) during infusion. However, neither drug altered collateral blood flow to the ischemic region during occlusion. In all three groups, left ventricular mass, area at risk mass, percentage of the left ventricle at risk, and retrograde flow during occlusion were similar. As compared with the control group, nicorandil reduced myocardial infarct size as determined by absolute mass, percentage of the area at risk infarcted, and percentage of the left ventricle infarcted. Nifedipine had no significant effect on infarct size. This beneficial effect of nicorandil was not related to an improvement in myocardial blood flow or a change in global hemodynamics.