Apo E phenotype was determined in 760 Belgian men, aged 35 to 59 years. Serum lipids and lipoproteins were related to the apo E polymorphism in 734 participants. By comparison with the most frequent apo E3/3 phenotype, the presence of the epsilon2 allele was associated with a lower serum total and non-HDL cholesterol, and with a lower apo B and a higher HDL cholesterol, independently of age, lifestyle factors and apo E concentration. In contrast, the presence of the epsilon4 allele was associated with a higher serum total and non-HDL cholesterol, and with a lower HDL cholesterol and a lower apo AI. The apo E phenotype explained 17.4% of the variance in apo E concentration; the proportion of the variance in total cholesterol, HDL cholesterol, apo AI and apo B levels explained by the apo E polymorphism was low but statistically significant. Among the lifestyle factors, waist to hip ratio was the only variable significantly associated with apo E concentration. The data suggest that besides the well-documented increasing effect on non-HDL cholesterol, the epsilon4 allele could further predispose to coronary heart disease through a decreasing effect on HDL while the epsilon2 allele could exert a protective influence through both a decreasing effect on non-HDL cholesterol and an increasing effect on HDL cholesterol.