To determine if apolipoprotein (apo) E polymorphism influences postprandial lipemia and hence can help explain the wide range of lipemic responses to a standardized fat meal observed previously, blood samples were collected from 25 healthy men whose postprandial responses to a standardized fat meal had been measured. Venous blood samples had been obtained before the fat meal (0.73 g fat/kg containing vitamin A) and hourly thereafter for 8 hours, plasma and chylomicron triacylglyceride (TAG) concentrations had been determined, and retinyl esters (REs) in the chylomicron and nonchylomicron fractions had been measured. The original results were reanalyzed by apo E phenotype (six E2/3; 14 E3/3; four E3/4 and one E4/4, grouped as E4). Contrary to what is known about the epsilon 4 allele, the apo E4 group displayed a significantly greater response curve than did either the apo E2/3 or E3/3 groups for both plasma TAG and chylomicron RE concentrations (p less than 0.01), as reflected in a later chylomicron RE peak for the apo E4 group (p less than 0.05). The E4 group tended (p = 0.18) to have a 40% higher fasting TAG than did either of the other groups, which may reflect bias in the selection of subjects. As fasting TAG is an important determinant in postprandial lipemia, results were normalized for this variable. After adjustment, the E4 group had the lowest TAG response relative to the E3/3 group (p less than 0.01). Our findings suggest that controlling for apo E phenotype may help to reduce interindividual variation in the postprandial response to a standard fat meal.(ABSTRACT TRUNCATED AT 250 WORDS)