Familial hypobetalipoproteinemia represents a heterogeneous group of genetic defects in which the concentrations of plasma apolipoprotein B and apo-B-containing lipoproteins VLDL and LDL are abnormally low. To explore potential effects of different genotypes on plasma lipid patterns, the lipoproteins of two families with hypobetalipoproteinemia were compared using zonal ultracentrifugation and chemical analyses. Heterozygotes differed between families not only in level and composition of apo-B-containing lipoproteins but also in HDL subclass distribution. In one family, heterozygotes had very low apo B levels and their major HDL subfraction was HDL2 as in abetalipoproteinemia, whereas in the second family heterozygotes had apo B levels approximately half on normal and the major HDL subfraction was HDL3 with an HDL elution pattern intermediate between that observed in abetalipoproteinemia and normal subjects. Observations on the HDL system in these two families substantiate the role of cholesteryl ester/triglyceride exchange between HDL and lower-density lipoproteins in the remodelling of HDL in plasma.