Coronary vasodilators have been variously reported to increase, decrease, or have no effect upon blood flow to ischemic myocardium. Consequently, the effects of two different types of dilators, nitroglycerin (TNG) and dipyridamole, were studied with radioactive microspheres in open-chested dogs after coronary artery ligation. Given as a bolus i.v. injection 0.4 mg TNG resulted in an increase in blood flow to nonischemic areas of myocardium and a preservation of flow to ischemic regions, despite a fall in blood pressure. 5 min later blood pressure and nonischemic flow were back to base line, and a small selective increase in flow to ischemic myocardium was found (0.15-0.18 ml/min per g, P less than 0.05). During an 0.2 mg/min infusion of TNG, and also after 1 mg/kg i.v. dipyridamole, ischemic flow was maintained in the face of a 20-30% reduction in blood pressure. In this setting, nonischemic flow was unchanged during TNG and doubled after dipyridamole. With the addition of methoxamine in both dilator groups, blood pressure returned to base line while flow to ischemic areas increased above base-line values (TNG, 0.16-0.20 ml/min per g, P less than 0.01; dipyridamole, 0.18-0.31 ml/min per g, P less than 0.05). Epicardial ST segment elevations increased during TNG infusion and were unchanged after dipyridamole, but with addition of methoxamine, ST segments became less elevated in both drug groups, concomitant with the observed increase in collateral blood flow. These data indicate that both types of coronary vasodilators, when used in conjunction with methoxamine to support blood pressure, reduce collateral resistance, increase collateral flow, and reduce epicardial ST-segment elevations.