We have evaluated a commercially available, standardized immunoturbidimetric assay of apolipoprotein (apo) A-I, the major protein constituent of high-density lipoproteins (HDL). We determined the reference ranges of plasma apo A-I concentration for white men and women and related these values to the risk of coronary heart disease (CHD). The mean between-run CV for this assay was 2.9%. As determined with individuals participating cycle 4 of the Framingham Offspring Study, the mean (+/- SD) apo A-I concentration was 13% lower in 1879 men (1.34 +/- 0.23 g/L) than in 1939 women (1.54 +/- 0.28 g/L) (P<0.001). An apo A-I concentration of 1.20 g/L roughly corresponded to the 25th percentile value in men and the 5th percentile in women, and subjects with a concentration below this value were significantly more likely to have CHD than subjects wit a higher concentration (P<0.001).