We studied the vasomotion of epicardial coronary arteries during exercise and tested the hypotheses that abnormal vasoconstriction is related to the presence of atherosclerosis and may be related to endothelial dilator dysfunction. During cardiac catheterization quantitative coronary angiography was performed in 21 patients during supine bicycle exercise. 21 of 28 smooth, angiographically normal vessel segments dilated (14.0 +/- 1.8%) during exercise; four smooth segments did not change whereas only three constricted. In contrast, 15 of 16 vessel segments with irregularities constricted in response to exercise (17.0 +/- 0.1%) with only one segment dilating. All 10 stenotic segments constricted to exercise (23 +/- 4%). Six patients also received intracoronary acetylcholine before exercise to test endothelium-dependent dilator function. In five of six patients all nine vessel segments showed the same directional response to acetylcholine and exercise. Three irregular and two stenotic segments constricted with acetylcholine (51 +/- 21%) and exercise (9.0 +/- 0.6%). In contrast, four smooth segments dilated to acetylcholine (19 +/- 6%) and exercise (9 +/- 1%). Both exercise and acetylcholine generally dilated smooth but constricted irregular and stenosed coronary segments. It appears likely that atherosclerosis plays an important role in the abnormal vasomotion of diseased coronary arteries during exercise and the pattern of abnormality suggests impairment of vasodilator function.