Cholesterol absorption was positively related to the apo E subscript in middle aged men on their normal home diet. The apo E subscript (e.g. E2/2 = 1, E2/3 = 2, E2/4 = 3...) was negatively associated with cholesterol synthesis and fractional removal of LDL apo B and positively with the total and LDL cholesterol and LDL apo B concentrations. Cholesterol elimination, especially as bile acids, was most effective in subjects with epsilon 2 allele. A slight reduction of biliary deoxycholic acid content in the men with the epsilon 4 allele and a negative correlation between deoxycholic acid and cholesterol absorption suggested that intestinal bacterial function may contribute to the positive association of cholesterol absorption to the apo E phenotype. Reduction of fat and cholesterol consumption lowered while an increase of dietary cholesterol enhanced the LDL cholesterol concentration proportionately to the apo E subscript when cholesterol absorption efficiency was reduced in proportion to fat intake. Low absorption, effective elimination and high synthesis of cholesterol associated with low synthesis and effective removal of LDL apo B seem to be factors keeping serum cholesterol low during different diets. The findings also suggest that the apo E phenotypes regulate cholesterol metabolism during basal conditions and serum cholesterol responses to dietary modifications.