Cigarette smoking is a major risk of coronary artery disease. Acetylcholine-induced coronary artery constriction has been reported in patients with normal coronary arteries and other risk factors. To evaluate coronary artery endothelial function in smokers, coronary artery responses to acetylcholine (10(-8) M to 10(-5) M) were analyzed by quantitative angiography in 5 young heavy-smokers and in 5 age-matched nonsmokers. All patients were normotensive, had normal left ventricular function and coronary arteries. Cholesterol, triglycerides, high- and low-density lipoproteins were within normal range. Vessel dimensions were measured on 4 segments of left coronary artery in all patients. In smokers, no change was produced at 10(-8) M and 10(-7) M acetylcholine concentration, but progressive diameter reduction was observed at 10(-6) M and 10(-5) M acetylcholine concentration. In nonsmokers, a dose-dependent dilation was produced from 10(-8) M to 10(-6) M acetylcholine concentration. No change was observed at 10(-5) M acetylcholine concentration. In the 2 groups, all segments dilated similarly after intracoronary isosorbide dinitrate. CONCLUSIONS This study reveals that in heavy-smokers the response of normal coronary arteries to acetylcholine is altered. Thus, endothelial dysfunction may be an early marker for coronary events in cigarette smokers.