Apolipoproteins B-100 and E are protein constituents of human plasma chylomicrons, very low (VLDL), and low density lipoproteins (LDL). The interaction of lipoproteins with cell receptors is mediated by apoB and E. Lipoproteins also bind to the extracellular matrix, such as glycosaminoglycans (GAG), forming insoluble complexes in the presence of Ca2+. The purpose of this study was to identify the GAG-binding domains in apoB and E. By a combination of fragmentation of the intact proteins, peptide synthesis and quantitative GAG-binding, domains in apoB and apoE were identified and are shown below. These domains contain clusters of basic amino acids that we suggest are required for GAG-binding. table; see text.