DNA sequences obtained from the mitochondrial cytochrome-b gene were used to evaluate phylogenetic relationships among 15 genera of putative neotomine–peromyscine rodents. Tree topologies obtained from maximum likelihood and Bayesian analyses revealed 4 primary clades that, in general, conform to the 4 tribes proposed by Carleton (1980). The Peromyscini (Megadontomys, Ochrotomys, Osgoodomys, Peromyscus, and Reithrodontomys) was sister to the Neotomini (Hodomys, Neotoma, Onychomys, and Xenomys). These 2 clades were then joined by the Baiomyini (Baiomys and Scotinomys) and Tylomyini (Nyctomys, Ototylomys, and Tylomys). The most apparent departure from previously proposed arrangements involved the placement of Onychomys in the Neotomini instead of the Peromyscini.