Serum concentrations for the cholesterol and triglyceride content of very low density lipoprotein (VLDL) and the cholesterol content of intermediate density lipoprotein (IDL), low density lipoprotein (LDL), and the high density lipoprotein fractions (HDL2), HDL3) were measured in 337 men and women with the apo E phenotype who were born in the Grampian Region of North East Scotland. The subjects' ages ranged from 45 to 60 years (mean, 53 years). Cigarette smoking and alcohol consumption were recorded and were shown to have minor, but suggestive, effects on serum lipoprotein concentrations. The LDL concentration of E-3/2 subjects was compared with the commonest category, E-3/3, and was found to be about 20% lower in men and about 12% lower in women, in whom the VLDL and IDL concentrations were substantially elevated. In E-4/3 women, the serum LDL concentration was about 10% higher than in E-3/3 women, and the other differences were minor. The effect of allelic substitutions differed between the sexes. The relations between C-peptide ratios and serum lipoprotein concentration differed by gender and phenotype. A comparison with earlier estimates of LDL heritability suggests that in this population, a substantial fraction of the genetic variance of LDL is due to segregation at the apo E locus. The implications of this significant finding are discussed.