Aortocoronary vein bypass surgery might not restore normal maximal coronary flow reserve to bypassed coronary vessels because residual diffuse coronary atherosclerosis might limit maximal hyperemia. To investigate the effect of diffuse atherosclerosis and a focal stenosis at the graft-coronary anastomosis, we measured coronary flow reserve with an extensively validated subselective Doppler catheter in 24 patients with 35 bypass grafts perfusing angiographically normal coronary vessels. The Doppler catheter was positioned in the midportion of the graft, and coronary flow reserve was measured as the peak/resting velocity ratio after selective graft injection of a maximally vasodilating dose of papaverine. Luminl dimensions of the bypass graft, graft-coronary insertion, and bypassed coronary vessel were measured by quantitative coronary angiography (Brown/Dodge method). Measurements of coronary flow reserve and coronary dimensions of vein bypass grafts were compared with similar measurements obtained from 13 patients with normal coronary vessels and normal myocardium. Seventeen of the 35 bypass grafts perfused unobstructed coronary-vein graft anastomoses (<50% area stenosis) and normal myocardium. The coronary flow reserve of these 17 bypass grafts was normal (5.0 ± 0.4, mean ± SEM) and not significantly different from that measured in normal arteries (5.1 ± 0.6), even though the cross-sectional area of the native coronary artery just distal to the bypass insertion was 40% smaller than in matched normal vessels. Bypass grafts perfusing hypertrophied (n = 2) or infarcted (n = 6) myocardium had significantly reduced coronary flow reserve compared with normal vessels (2.7 ± 0.3; p < .01), even when the infarcted wall had only minimal hypokinesis. In grafts perfusing normal myocardium, coronary flow reserve was significantly correlated with a minimum cross-sectional area of the graft at the point of coronary insertion (r = .77) and the percent area stenosis of the graft-coronary insertion (r = .77). All bypass grafts having lesions at the graft-coronary insertion producing less than 50% area stenosis or with greater than 2.0 mm2 minimum cross-sectional area had normal coronary flow reserve. These results demonstrate that myocardial revascularization with an aortocoronary vein bypass graft restores a normal maximal flow reserve capacity to the perfusion field of the graft, provided that the graft perfuses a nonstenotic coronary vessel and normal myocardium. These findings suggest that moderate, diffuse coronary atherosclerosis does not significantly impair maximal coronary flow reserve. Moreover quantitative angiographic measurements may be useful in predicting the functional significance of lesions at the graft-coronary anastomosis.