Increasing blood flow results in endothelium-dependent vasodilation of angiographically normal epicardial coronary arteries in humans. To compare the ability of internal mammary artery (IMA) and saphenous vein (SV) used as coronary artery bypass grafts to adapt their vasomotor tone to an increase in myocardial blood flow demand induced by tachycardia, 10 IMA and seven SV grafts were studied by quantitative angiography more than 6 months (range, 6-82 months) after surgery in 17 patients. All grafts were angiographically smooth and implanted to large nonakinetic perfusion zones. Angiograms were obtained in basal sinus rhythm (71 +/- 10 beats/min), during atrial pacing (129 +/- 9 beats/min), and after intragraft infusion of 1 mg isosorbide dinitrate (ISDN). In basal sinus rhythm, the cross-sectional area of SV was superior to that of IMA (10.7 +/- 3.6 versus 5.4 +/- 1.7 mm2; p less than 0.01). All IMA dilated during pacing (+14.8 +/- 11.5%; p less than 0.005) and a further increase in IMA cross-sectional area occurred after ISDN (+27.4 +/- 20.1% versus basal; p less than 0.005). In contrast, SV failed to dilate during pacing (+0.3 +/- 5.4%; p = NS) and after ISDN (+0.7 +/- 6.0% versus basal; p = NS). Thus, an increase in myocardial blood flow demand induced by tachycardia results in dilation of IMA but not of SV grafted on coronary vessels. The ability of the endothelium to modulate the vasomotor tone of IMA grafts in response to changes in blood flow could contribute to their excellent long-term functional results after coronary artery bypass surgery.