Background. Exercise-induced dilation of coronary resistance vessels is limited by alpha-adrenergic mechanisms. However, the effect of alpha-adrenergic mechanisms on large coronary arteries during exercise is not known. Methods and Results. In the present study, sonomicrometry was used to measure circumflex coronary arterial diameter during treadmill exercise before and after alpha(1)-adrenergic blockade with prazosin in eight instrumented dogs. Before infusion of prazosin, exercise caused a fall in coronary vascular resistance (2.1 +/- 0.4 to 1.6 +/- 0.2 units, p < 0.05) and dilation of the circumflex coronary artery (4.66 +/- 0.37 to 4.79 +/- 0.34 mm, p < 0.05). Intracoronary infusion of prazosin during exercise caused a further decrease in coronary vascular resistance (1.6 +/- 0.2 to 1.4 +/- 0.2 units, p < 0.05) and a further increase in circumflex coronary arterial diameter (4.79 +/- 0.34 to 4.83 +/- 0.34 mm, p < 0.05). Intracoronary infusion of vehicle without prazosin during exercise did not cause a further decrease in coronary vascular resistance or increase in coronary diameter. Prazosin caused no significant increase in heart rate, aortic pressure, or coronary blood flow. Therefore, both small coronary resistance vessels and large epicardial coronary arteries dilated during exercise and dilated further after alpha-adrenergic blockade. Conclusions. This finding indicates that alpha(1)-adrenergic activity during exercise limits dilation of both large and small coronary arteries.