The mature peptides are cationic and amphipathic, which are important properties for inducing the depolarization and permeabilization of the microbial membrane. The a-defensin monomer has a three-stranded antiparallel b-sheet structure with three intramolecular disulfide pairs linked as Cys1-Cys6, Cys2-Cys4 and Cys3Cys5. Two monomers form an amphipathic dimer, which is stabilized Alisol-B by hydrophobic interactions and intermolecular hydrogen bonds between residues 18 and 20 in the second b-sheet. The dimerization of a-defensins, in addition to their cationic and amphipathic character, is also important for their antimicrobial ability. In contrast to the structure of a-defensins, the h-defensins form a cyclic octadecapeptide through the posttranslational head-to-tail ligation of two nonapeptides and harbor three intermolecular disulfide pairs. Recently, synthetic defensins have been studied and are being developed as potential antimicrobial peptide drugs. Because of the frequent duplication and rapid evolution of primate a-/h-defensins, the nomenclature and phylogenetic relationships among this multigene family Alisol-A are still ambiguous. Moreover, there is no clear phylogenetic classification related to the expression pattern or the confounding antimicrobial function of these a-defensins, although many functional studies indicate that a-defensins are effective microbicidal peptides against a wide variety of microorganisms. Previous studies have demonstrated that the a-/h-defensin multigene family, like many other multigene families, is subject to birth-and-death evolutionary process with frequent gene duplication, pseudogenization and significant positive selection. However, the molecular evolution of the undocumented antimicrobial spectra that are composed of functionally divergent a-/h-defensins in humans and closely related primates should be further explored. In this study, the phylogenetic classification, sequence divergence and structural diversification of the primate a-/h-defensins were investigated using molecular evolution and molecular dynamics analyses.