Recent studies have demonstrated that elevated levels of cholesterol in the form of remnant-like particles (RLP-C) induce deterioration of endothelial function during the fasting state, but it is not known whether postprandial RLP-C elevation has the same effect. The objective of this study was to assess the effect of postprandial RLP-C elevation on endothelial function in 24 fasting normolipidemic subjects. Flow-mediated dilatation (FMD) during reactive hyperemia in the brachial artery was investigated. Serum lipids and lipoproteins during fasting and 4h after regular fat-loading were measured. Subjects were divided into 2 groups: the high responders (postprandial RLP-C level >7.5mg/dl, n=8) and the normal responders (postprandial RLP-C level < or =7.5mg/dl, n=16). Significant increases in the level of both triglycerides and RLP-C were observed in the high responders. Basal FMD in the high responders (4.3+/-3.0%) was significantly lower than that in the normal responders (8.3+/-2.4%) (p<0.01), but FMD after the fat-loading in both groups did not change significantly. The change in RLP-C levels during the fat-loading test correlated significantly with basal FMD (r=-0.588, p<0.01). Multiple regression analysis showed a significant correlation between basal FMD and the change in RLP-C levels (r=-0.488, p<0.02). The results of this study suggest that postprandial RLP-C elevation could be associated with atherosclerotic progression even in normolipidemic subjects.