The effects of nitroprusside (NP), phentolamine (PH), and nitroglycerin (NTG) were studied on systemic hemodynamics, regional contraction and epicardial ST segment in the border and non-ischemic zones of the left ventricle of anesthetized open chest dogs. The anterior descending coronary artery (LAD) was completely occluded. NP (5 microgram/Kg/min) or PH (100 microgram/Kg/min) was drip-infused, or a bolus injection of NTG (20 microgram/Kg) was administered intravenously. The 3 vasodilator agents produced somewhat similar reductions in systemic arterial pressure. However, NP caused a greater reduction in total peripheral resistance (TPR) than in left ventricular end-diastolic pressure (LVEDP), and caused a decline, in the ischemic marginal zone, in both ST segment eievation and paradoxical systolic lengthening. PH decreased TRP without reducing LVEDP and elevated the ST segment. NTG markedly reduced LVEDP and TPR slightly. NTG improved the elevated ST segment and paradoxical systolic expansion of the segmental myocardium in the border zone. Cardiac output rose with NP and PH, whereas injected NTG caused a reduction in cardiac output. These findings suggest that NP favourably affects the ischemic myocardium mainly by reducing the afterload and that the NTG-induced improvement of myocardial ischemia can be attributed mainly to preload reduction, while PH enhances cardiac function with slight or no improvement of myocardial ischemia in the border zone.