The compositional and metabolic heterogeneity of operationally defined plasma lipoprotein classes (1-3) has necessitated the introduction of a classification system that utilizes apolipoproteins as specific markers for identifying and distinguishing discrete lipoprotein particles (1,4). In this system, lipoprotein particles are characterized and defined by their apolipoprotein composition (1,4). Studies on the quantification and distribution of apolipoproteins (4,5) have shown that apolipoprotein (Apo)B and ApoA (A-I 4- A-II) form two major groups of plasma lipoproteins. These two major lipoprotein groups may be separated (6) by immunoprecipitation or immunoaffinity chromatography of whole plasma (6). The use of these procedures results in the isolation of ApoA-containing lipoproteins free of ApoB. The fractionation of ApoA-containing lipoproteins into two major discrete lipoprotein particles LP-A-I and LP-A-I:A-II by immunoaffinity chromatography on an immunosorber with polyclonal antibodies to ApoA-II has already been described by Cheung and Albers (7). To identify discrete lipoprotein particles of the ApoB group of lipoproteins, we have developed a procedure based on sequential immunoprecipitation of ApoB-containing lipoproteins with polyclonal antisera to apolipoproteins B, E, C-III and, if necessary, C-II and C-I (6,8). The fractionation of very low density (VLDL, d < 1.006 g/ml) and two subtractions of low density (LDL.., d = 1.006-1.019 g/ml; LDL?, d = 1.019-1.063 g/ml lipoproteins from normolipidemic subjects by sequential immunoprecipitation showed that each of these density classes consists of a mixture of distinct lipoprotein particles including cholesterol ester-rich LP-B and triglyceride- rich LP-B:C-I:C-II:C-III:E (LP-B:C:E) and LP-B:C-I: C-II:C-III (LP-B:C) particles (8). The LP-B:C:E family of particles in some normolipidemic and hypercholesterolemic subjects also contained varying amounts of LP-B:E particles. In addition, small amounts of LP-B:C-I:E, LP-B:C-II, LP-C-III and LP-E particles were detected in some but not all-subjects or density classes. Each of the major ApoB-containing families of particles was shown to represent a polydisperse system of particles heterogeneous with respect to size, hydrated density, and lipid/protein ratio, but homogeneous with respect to the qualitative apolipoprotein composition.