Recent advances in molecular biology provide measures of genotypes at loci involved in lipid metabolism. Genotypes for apolipoprotein E (apo E) and quantitative levels of total plasma cholesterol, betalipoprotein, and triglycerides were measured in a sample of 223 unrelated individuals from Nancy, France. The frequencies of the epsilon 2, epsilon 3, and epsilon 4 alleles are 0.13, 0.74, and 0.13, respectively, in this sample. Significant differences among apo E genotypes were detected for these lipoprotein phenotypes. The average effect of the epsilon 2 allele was to reduce total plasma cholesterol and betalipoprotein levels by 0.52 mmol/L and 0.98, respectively, while the epsilon 4 allele raised these levels by 0.26 mmol/L and 0.61, respectively. Apo E genotype specific correlations suggest that this locus also has an effect on the coordinated metabolism between cholesterol and triglycerides. We infer that approximately 17% of the genetic variability in total plasma cholesterol may be attributable to this apo E polymorphism. No other single locus has been identified with such a large contribution to cardiovascular disease risk factors in the general population.