Immunoturbidimetric assay for the determination of serum apolipoprotein E was developed on the Cobas-BIO centrifugal analyzer using commercially available antisera and reference sera. Within-run imprecision was 2.9% while day-to-day imprecision was 7.9%. Addition of up to 50 g/l hemoglobin or 0.15 g/l bilirubin to sera did not interfere with the determination of this apolipoprotein. Apolipoprotein E concentration was measured in sera from 40 normolipidemic and hyperlipidemic subjects by this immunoturbidimetric method (dependent variable) and radial immunodiffusion assay (independent variable). A slope of 0.90, an intercept of -7.9, and a correlation coefficient of 0.94 were obtained. Reference range for apolipoprotein E was established using sera from 100 normolipidemic subjects. The mean + 1 SD for apolipoprotein E levels of males and females were 36 + 13 mg/l and 29 + 8.4 mg/l, respectively. The distribution of apolipoprotein E among the various lipoprotein fractions of normals was significantly different than that of hypertriglyceridemic subjects.