ApoA-IV is one of the major protein components of rat chylomicrons and HDL and is also associated with chylomicrons in humans and dogs; however, the precise metabolic function of this protein remains obscure. This chapter presents a computer program appropriate to study protein and nucleic acid sequences, the critical interpretation of the results that can lead to specific and experimentally testable predictions of a protein's structure and function, and may yield insights into its evolution and the location of its gene. The chapter demonstrates that rat apoA-IV bears a striking structural similarity to human apoA-I. Statistical analyses of homologies between apolipoproteins A-I, A-IV, and E show that all three sequences diverged from a common ancestral gene. Assuming that the genes for these proteins had evolved as a result of a series of intra- and intergenic unequal cross-overs, it is likely that their genetic loci were at one time linked. Given this fact, the existence of other genes or pseudogenes based upon this repeated sequence motif is a distinct possibility.