An acute oral fat load produces transient lipemia that is enhanced by the simultaneous ingestion of ethanol. This phenomenon has been reinvestigated in six normal subjects who consumed three different fat loads with and without ethanol. The fat loads consisted of saturated fat, polyunsaturated fat, or polyunsaturated fat enriched with omega-3 (n-3) fatty acids. Each fat load contained retinol as a marker for intestinally derived lipoproteins. Plasma levels of triglycerides, retinyl palmitate, and nonesterified fatty acid species were determined at several time points after consumption. Increasing the size of a saturated fat load increased postprandial lipemia and delayed retinyl palmitate clearance. Postprandial lipemia and plasma retinyl palmitate concentrations were lower when omega-3 or omega-6 (n-6) polyunsaturated fat was substituted for saturated fat. Preprandial ethanol increased postprandial lipemia, an effect that was most profound with the saturated fat load. Concurrently, oral ethanol also increased postprandial retinyl palmitate. Addition of ethanol to the fat loads had no effect on the plasma concentrations of fatty acids derived from peripheral tissue but appeared to decrease the plasma concentration of free fatty acids of dietary origin. These data support the hypothesis that preprandial ethanol is associated with impaired chylomicron hydrolysis that may be due to inhibition of plasma lipoprotein lipase. These findings are important to the search for the molecular mechanism of ethanolic hypertriglyceridemia and to the development of dietary guidelines for its control.