BACKGROUND AND PURPOSE: It has been suggested that a postprandial accumulation of triglyceride-rich lipoproteins promotes the development of atherosclerosis. This study was designed to test the hypothesis that postprandial lipemia is independently associated with intima-media thickening of the extracranial carotid arteries. METHODS: Forty-seven middle-aged, moderately hypercholesterolemic individuals were recruited for a 1-day study of the lipemic response to a standard high-fat test meal. The formula was fed at a dose of 65 g fat/m2 body surface area, after a 14-hour fast, and blood was obtained for triglyceride analysis hourly for 8 hours. A baseline lipid profile was obtained. Each subject underwent a carotid ultrasound examination. The extent of alimentary lipemia (peak triglyceride response) was correlated with the carotid artery wall thickness as measured by B-mode ultrasound. RESULTS: Univariate analyses indicated an inverse correlation between peak triglyceride response and high density lipoprotein cholesterol concentration and a direct correlation with male sex, baseline triglyceride concentration, background fat intake, and waist-to-hip ratio. Of these, the only variable that showed a univariate correlation with B-mode score was peak triglyceride response. Age and cigarette smoking were also correlated with B-mode score in univariate analyses. The correlation coefficient (r = 0.52) between peak triglyceride response to a fat-rich meal and B-mode score was significant (p less than 0.002) and remained so in multivariate analysis. Forward-selection stepwise regression resulted in the inclusion of only peak triglyceride response (p = 0.001) and smoking history (p = 0.005) as important predictors of carotid wall thickness in a linear model. CONCLUSIONS: The association between lipemic response and carotid wall thickness suggests that prolonged exposure of arterial wall cells to triglyceride-rich chylomicron remnants enhances the atherogenic process.