1. Low-density (d 1.006-1.063 g/ml) lipoproteins from normal human plasma were separated by differential preparative ultracentrifugation into six subfractions. Each lowdensity (LD)lipoprotein subfractioncontained lipoprotein B as the major andlipoproteins A and C as the minor lipoprotein families. 2. Three lipoprotein B subfractions (LP-B), LP-B-III (d 1.019-1 .030g/ml), LP-B-IV (d 1.030-1.040g/ml) and LP-B-V (d 1.040-1.053 g/ ml) were prepared from the corresponding LD lipoprotein subfractions by immunoprecipitating small amounts oflipoproteins A and C. 3. Determination of hydrodynamic properties indicated that LD lipoproteins consisted of three molecular segments characterized by a stepwise change in the molecular weight: LDL-I and LDL-II subfractions (d 1.006-1.019g/ml) with an average mol.wt. of 4.75 x 106, LDL-III (d 1.019-1.030g/ml) with a mol.wt. of 3.99 x 106, and LDL-IV, LDL-V and LDL-VI (d 1.030-1.053g/ml) with a mol.wt. of 2.85 x 106. 4. All three lipoprotein B subfractions had an average mol.wt. of 3.16 x 106. 5. The LDL-I and LDL-II subfractions consisted of lipoprotein B and lipoprotein C families which were present in the form of an association complex. This was isolated from serum by immunoprecipitation with antibodies to lipoprotein B. The complex had a mol.wt. of 4.35 x 106. 6. The results indicate a fundamental difference between the LD lipoprotein subfractions with d 1.006-1.019g/ml and those subfractions with d 1.030-1.063g/ml. In the former, lipoprotein B occurs as a part of an association complex, whereas in the latter it occurs as a separate entity.Human plasma low-density lipoproteins consist of two macromolecular distributions characterized by Sf 0-12 and Sf 12-20 (Oncley, 1963;Ewing et al., 1965;Nichols, 1967). The heterogeneity of both subclasses in regard to particle size, hydrated density and molecular weight has been attributed to discrete changes in the lipid and protein content of the lipoprotein molecules (Oncley etal., 1957;Shore & Shore, 1962;Nichols, 1967;Dearborn & Wetlaufer, 1969