AbstractSome of the component moieties of high denisty lipoproteins (HDL) were analyzed in normal subjects and in patients with hyperlipidemia. Apoproteins A‐I and A‐II were quantified by radioimmunoassay, HDL cholesterol and triglycerides were assessed on heparin‐MnCl2 supernates of fasting plasmas. We found that HDL is enriched in triglycerides in all forms of hyperlipidemia, while the proportion of ApoA‐II is unaltered and the proportion of ApoA‐I is decreased. Thus, the composition of HDL is altered in hypertriglyceridemia. The molecular associations of ApoA‐I and ApoA‐II in plasma were also examined by assaying the apoprotein contents of plasma fractions prepared by ultracentrifugation and by gel filtration column chromatography. The ApoA‐I contents of d<1.063 fraction increased in hyperlipidemia from <0.5% to ∼2%, but the ApoA‐I contents of the d>1.21 fraction remained at <12% of total in plasmas with triglyceride levels <1500 mg/dl. d>1.21 ApoA‐I rose to 23% in one plasma with a triglyceride level of >1700 mg/dl. On column chromatography, ApoA‐I eluted with the lipoproteins and also in a fraction whose molecular weight (MW) appreared to be ∼50,000 daltons. The proportion of plasma ApoA‐I which eluted in the 50,000 MW peak was positively correlated with plasma triglyceride levels, but at triglyceride levels of <1500 mg/dl, <20% of ApoA‐I was in the 50,000 MW peak. Between levels of ∼2000 and 12,000 mg/dl, the percentage “50,000 M.W. ApoA‐I” was 20–25%. The ApoA‐II contents of d<1.063 fractions were also increased in hyperlipidemia, but >95% of ApoA‐II was found in the HDL fractions in both normal and hyperlipidemic plasma both by column chromatography and ultracentrifugation. Thus, the molecular association of ApoA‐I appears to be altered in hyperlipidemia.