Apolipoprotein E (apo E) phenotypes have been previously shown to influence plasma lipoprotein concentrations in normal populations and to affect the response to some lipid lowering drugs. The purpose of the present study was to determine if variations in the apo E phenotype also affect basal lipoprotein concentrations in patients with heterozygous familial hypercholesterolemia (FH) and if the apo E phenotype influenced their subsequent response to lovastatin. Apo E phenotypes were determined on plasma from 134 FH patients. The relative frequencies of the epsilon 2, epsilon 3, and epsilon 4 alleles were .090, .772, and .138, respectively. Plasma triglycerides were found to be 34% higher in E3/2 heterozygotes relative to E3/3 patients. Baseline concentrations of low-density lipoprotein (LDL) cholesterol in untreated FH patients were not influenced by the apo E phenotype; the hypolipidemic response to lovastatin (20 or 40 mg twice daily) was also independent of the apo-E phenotype of the patients.