A sensitive and specific enzyme-linked immunosorbent assay (ELISA) for human apolipoprotein E (apo E) quantification using commercially available reagents is described. The assay is a noncompetitive, sandwich ELISA in which the wells were coated with a monoclonal EO1 antibody anti-human apo E and detected with a polyclonal antibody-peroxidase conjugate anti-apo E. The mean apo E concentration in 168 middle-aged subjects randomly selected from general population was 51.7 +/- 12.4 mg/liter. Apo E levels were highly correlated with apo E phenotypes. Apo E polymorphism, which shows a modulating effect in the catabolism of apo E containing lipoproteins, may explain a large fraction, 18.5%, of the variability of serum apo E levels in middle-aged population. Isoforms apo E2 and apo E4 have an opposite effect on the regulation of serum apo E concentrations. Individuals that express apo E2 isoform present higher apo E levels (65.5 mg/liter for apo E2/E3), whereas the average of individuals with apo E4 is lower (42.8 mg/liter for apo E4/E3) than general population.