Hypobetalipoproteinemia in many kindreds is associated with truncated forms of apoB-100. Mutations of the apoB gene specifying more than 20 different carboxyl terminal truncations of apoB have been identified ranging in length from apoB-2 to apoB-89. Truncations longer than apoB-48 appear to be secreted only by liver, while truncations shorter than apoB-48 are secreted by liver as well as intestine. Thus, intestines of subjects heterozygous for truncations > apoB-48 contain two alleles producing apoB-48, while intestines of heterozygotes with truncations < apoB-48 contain only one allele producing apoB-48. Our aims were to assess whether intestinal fat absorption differed from normal in subjects with apoB-truncation-associated hypobetalipoproteinemia and whether fat absorption in heterozygotes with apoB < 48 differed from heterozygotes with apoB > 48. Ten subjects heterozygous for apoB > 48 (apoBs -89, -75, -54, -52), six heterozygous for apoB < 48 (apoBs -46, -40, -31) and a group of 16 controls matched for age, sex, body mass index characteristics, and eating similar diets were given identical fat meals containing vitamin A. Plasma triglycerides in whole plasma and retinyl palmitate in chylomicron and non-chylomicron (remnant) fractions were analyzed at zero time and over the next 14 hours. Fasting vitamins A and E also were quantified. Fasting plasma levels of vitamin E were lower in heterozygotes (536 +/- 198 mg/l for apoB > 48 vs. 372 +/- 155 for apoB < 48) versus controls (1162 +/- 441), but were not different when corrected for differences in LDL-C. Plasma vitamin A levels (uncorrected) were not different. Meal responses were characterized in terms of peak concentrations and areas under the curves (after subtraction of minimum points). These indices of fat absorption were comparable in all apoB phenotype groups suggesting that one allele specifying the intestinal production of apoB-48 is sufficient for normal fat absorption.