Low concentrations of high-density lipoprotein cholesterol (HDL-C) have been associated with increased risk of coronary heart disease (CHD) even when the total cholesterol (TC) and triglyceride (TG) levels are not elevated. The mechanism by which HDL confers protection against atherosclerosis remains speculative. Using high-resolution ultrasound, we measured the dilatation changes of brachial arteries during reactive hyperemia and after sublingual glyceryl trinitrate (GTN) in 63 patients with established (CHD) and 45 controls, in which the serum TC level was normal. The results showed that both flow-mediated dilatation (FMD) and GTN-induced dilatation of brachial arteries in patients with CHD were much reduced compared with control group (2.31+/-2.46% vs. 7.43+/-4.10% and 16.41+/-6.15% vs. 22.44+/-8.63%, respectively, P<0.001 for all). Univariate analysis indicated that FMD of brachial arteries was inversely related to age (r=-0.226, P<0.05), hypertension (r=-0.229, P<0.05), baseline diameter (r=-0.299, P<0.01) and LDL-C (r=-0.237, P<0.05) and positively related to HDL-C (r=0.491, P<0.01). GTN induced vasodilatation was inversely related to age (r=-0.216, P<0. 05) and baseline diameter (-0.476, P<0.01). Multiple stepwise regression analyses in two groups taken together showed that HDL-C and age were the independent predictors of the FMD of brachial arteries (beta=0.466, P=0.000 and beta=-0.184, P=0.020, respectively). Baseline diameter was significant predictor of GTN-induced vasodilatation (beta=-0.390, P=0.000). The analysis in the group of CHD patients showed that only HDL-C was significantly relate to the FMD of brachial arteries (beta=0.295, P=0.018 ) and in controls that hypertension and HDL-C were significantly relate to the FMD of brachial arteries (beta=-0.395, P=0.004 and beta=0.344, P=0.011, respectively). These finding suggest that endothelium-dependent and endothelium-independent vasodilatation are impaired in the patients with CHD. HDL exerts a protective effect on endothelium-dependent vasodilatation in TC being relatively normal population.