Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder associated with hypercholesterolemia, in which substitution of the amino acid glutamine for arginine at position 3500 in the apoprotein B molecule results in LDL particles which bind poorly to the LDL receptor. To date, patients with FDB have been heterozygous for this disorder and their plasma contains both normal and defective-binding LDL particles, with a predominance of the latter. In the present report, we have compared the hypocholesterolemic effects of bile acid sequestrant therapy (cholestyramine or colestipol) in eight patients with FDB, to the response seen in sixteen patients with heterozygous familial hypercholesterolemia (FH), treated with the same drugs. Concentrations of LDL cholesterol fell by 32.0% in the patients with FDB and by 21.6% in the patients with FH. The results indicate that the hypercholesterolemia of both FDB and FH responds to treatment with bile acid sequestrants.