Ordinarily, HDL1, a fraction of HDL enriched in apoE, is a minor fraction of plasma, but in human subjects and experimental animals eating diets high in fat and cholesterol and in patients with homozygous familial hypercholesterolemia (HFH) or CETP deficiency, HDL1 (or HDLc) concentrations in plasma are increased. However, little is known about the structures, compositions and metabolic sources of HDL1 in HFH patients. To obtain HDL1 for the study, we surveyed several fractions in the HDL density range for apoE by SDS-PAGE. The ratio of apoE to apoAI in the HDL (d = 1.063-1.21 g/ml) of 8 HFH patients was 0.14 +/- 0.03 compared to 0.03 +/- 0.005 in a control group of 8 normolipidemic subjects (P less than 0.001) suggesting that an apoE-rich fraction indeed was present in increased amounts. ApoE/apoAI ratios of lipoproteins of the density range 1.050-1.090 were even higher at 1.5 and 2.0 in 2 patients compared to 0.4 +/- 0.1 in controls, indicating that this density fraction may be particularly enriched with apoE-rich lipoproteins. By contrast, d = 1.020-1.050 g/ml and d greater than 1.090 fractions contained very little apoE. Therefore, we further characterized the d = 1.050-1.090 g/ml lipoproteins of HFH patients and controls. Fractionation of an d = 1.050-1.090 fraction by concanavalin-A chromatography (CONA) yielded an unbound apoE-rich fraction that contained apoE, apoAI and apoC but no apoB, and a bound LDL-like fraction that contained mostly apoB-100, as determined by SDS-PAGE and by solid phase immunoassays, containing monoclonal antibodies directed against apoB, apoE and apoAI. The apoE/apoAI ratio of the CONA unbound fraction of HFH patients was greater, and the fraction also contained more free cholesterol and phospholipids than the fraction of control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)