Endothelium-dependent vasomotor responses differ in arteries and veins. The transfer of a given vessel from a different vascular bed into the coronary circulation by grafting may affect its endothelial function. In order to evaluate the differences in endothelial function of the internal mammary artery and aortocoronary venous grafts in patients with coronary artery disease, the response to acetylcholine (ach) was examined and compared with that of native coronary arteries. Eighteen patients were examined, including eight with internal mammary artery grafts (9 days to 48 months after surgery), and 10 with saphenous vein grafts (12-96 months after surgery). Ach (70-700 nmol min-1) was infused selectively into a graft on the left anterior descending coronary artery, and the effect on vessel diameters was assessed by quantitative arteriography. In both groups 84% and 83%, respectively, of the arterial segments distal to the bypass anastomosis were contracted by ach (greater than or equal to 70 nmol min-1). The segments of both groups did not show angiographic evidence of local atherosclerosis. A complete occlusion occurred in four cases. In contrast, internal mammary artery grafts were not contracted by ach; in four of 12 segments a dilatation was observed, whereas five of 20 aortocoronary venous graft segments showed a slight reduction in lumen diameter after the highest ach dose applied. The vasoconstricting effect of ach was reversed by intracoronary nitroglycerin. By using ach as an indicator of endothelial dysfunction it is concluded that the internal mammary artery grafts maintained an intact endothelial function after surgery, whereas the coronary artery segments showed an impaired endothelium-dependent vasodilatation. Some of the venous graft segments reacted as coronary arteries did with a less pronounced cholinergic vasoconstriction. This in vivo study supports the observation of a functional superiority of internal mammary artery over saphenous vein coronary grafts.