Allelic variation within the mouse androgen-binding protein (ABP) α subunit gene (Abpa) has been suggested to promote assortative mating and thus prezygotic isolation. This is consistent with the elevated evolutionary rates observed for theAbpagene, and theAbpbandAbpggenes whose products (ABPβ and ABPγ) form heterodimers with ABPα. We have investigated the mouse sequence that contains the threeAbpa/b/ggenes, and orthologous regions in rat, human, and chimpanzee genomes. Our studies reveal extensive “remodeling” of this region: Duplication rates ofAbpa-like andAbpbg-like genes in mouse are >2 orders of magnitude higher than the average rate for all mouse genes; synonymous nucleotide substitution rates are twofold higher; and theAbpabggenomic region has expanded nearly threefold since divergence of the rodents. During this time, one in six amino acid sites in ABPβγ-like proteins appear to have been subject to positive selection; these may constitute a site of interaction with receptors or ligands. Greater adaptive variation amongAbpbg-like sequences than amongAbpa-like sequences suggests that assortative mating preferences are more influenced by variation inAbpbg-like genes. We propose a role for ABPα/β/γ proteins as pheromones, or in modulating odorant detection. This would account for the extraordinary adaptive evolution of these genes, and surrounding genomic regions, in murid rodents.