Triglyceridemic response to a standard oral fat meal was determined in 28 healthy subjects and related to the levels of several lipids, lipoproteins, and apolipoproteins in the postabsorptive plasma. A fatty test meal was administered orally, and postprandial plasma triglyceride levels were determined. In the fasting blood samples, concentrations of apolipoproteins (apo) A-I, A-H, and B were determined by radioimmunoassay, and those of high density lipoprotein (HDL) subfractions HDL2 and HDL3, by zonal ultracentrifugation. The magnitude of triglyceridemic response showed a negative correlation with the plasma levels of HDL2 (r = -0.860, P < 0.001), HDL-associated cholesterol (r = -0.605, P < 0.001), and apoA-I (r = -0.459, P < 0.02). No correlation was found between the triglyceridemic response and the levels of total cholesterol, HDL3, and apoA-II. Triglyceridemic response was correlated positively with fasting triglyceride concentrations (r = 0.450, P < 0.02) and apoB levels (r = 0.396, P < 0.03). In two subjects followed for 3 yr, when HDL2 levels rose or fell, the triglyceridemic response decreased or increased, respectively (r = -0.944; r = -0.863). Our data indicate that normolipidemic individuals with high HDL2 levels in the plasma are able to clear alimentary fat at a faster rate than normolipidemic subjects with low HDL2 levels. The pronounced difference in severity and duration of postprandial lipemia among subjects with varying HDL2 levels may help to explain the negative correlation between the risk of atherosclerosis and HDL cholesterol levels.Atherosclerosis is the major underlying cause of death and disability in western society. Virtually all epidemiologic studies to date have shown that enhanced serum cholesterol values at the time of entry into the study are predictors for the development of coronary heart disease (1). The importance of triglyceride as a risk factor is currently a matter of dispute (2,3). Increases of low density lipoproteins (LDL) predispose to premature coronary heart disease (4), whereas the high density lipoproteins (HDL) have been found to have a powerful inverse correlation with coronary heart disease (5-7). Although a causal relationship can be established both in man and in experimental animals for increases of LDL and atherosclerosis (8), none have yet been established for HDL.HDL consist of two major subfractions, HDL2 and HDL3 (4). The former lipoproteins are larger in size, contain more lipid, and have a lower density (9). HDL2 contain predominantly apolipoprotein A-I (apoA-I), with relatively little apoA-II, whereas HDL3 contain appreciable quantities of both of these proteins (10-12). The most striking difference in plasma lipoproteins between males and females lies in the levels of HDL2, which are roughly 3 times higher in females than in males (4,8). In hyperalphalipoproteinemia, a familial condition that provides protection against coronary heart disease (13), the primary increase occurs in HDL2 (14). Physical exercise increases the concentrations of ...