Background: In patients with typical angina but angiographically normal coronary arteries, abnormal vasomotor function is assumed to be a major underlying cause. However, data on this issue are conflicting, and recent studies suggest that fluid dynamic abnormalities exist in these patients. The aim of the study was to evaluate whether early stages of atherosclerosis are characterized by alterations of baseline coronary hemodynamics and endothelium-independent vasomotion. Besides established intracoronary Doppler parameters, heterogeneity of perfusion was assessed and related to early signs of atherosclerosis as determined by electron-beam computed tomography (EBCT). Methods: In 59 patients with typical angina and angiographically normal or near-normal coronary arteries, intracoronary Doppler measurements were performed in all 3 major coronary arteries. Baseline average peak velocity (bAPV) and hyperemic average peak velocity (hAPV) in response to intracoronary injection of adenosine were measured, and coronary flow velocity reserve (CFVR) was calculated. Heterogeneity was assessed as variability of bAPV, hAPV, and CFVR and was calculated as (STD/MEAN). 100. Doppler data were analyzed according to tertiles of the EBCT-derived Agatston calcium score (ie, score 0-1 [lowest tertile], 2-28 [medium tertile], and >28 [highest tertile]). Results: The mean EBCT-derived Agatston calcium score was 49 ± 107. No coronary calcium was observed in 17 (29%) patients. The mean values of bAPV, hAPV, and CFVR were not different between the calcium score tertiles. However, patients in the highest tertile had a significantly increased variability index of bAPV (29.6% ± 11.6%) compared with patients in the lowest tertile (13.4% ± 7.3%, P < .0001). Variability of CFVR was also increased in these patients (15.5% ± 11.7% vs 10.5% ± 4.0%, P = .03). Conclusion: These results indicate that early stages of atherosclerosis are characterized by microvascular abnormalities that do not uniformly affect the myocardium but are heterogeneous. The high variability of baseline coronary flow velocity with increasing coronary calcium suggests that in patients with early stages of atherosclerosis fluid dynamic effects may play a crucial role even in the absence of angiographically appreciable epicardial stenoses.