The role of apo-E in mediating lipoprotein interaction with specific receptors has been established. Through the use of selective chemical modification of specific amino acid residues of certain lipoproteins, we have gained insight into the importance of the lysine and arginine residues in this process. This understanding has been expanded by structure-function studies of mutant forms of apo-E. These studies have revealed important information concerning the genetic heterogeneity of the apo-E isoforms, focusing attention on the importance of a specific region of apo-E in the binding process.