Peromyscus melanophrys is a Mexican endemic distributed in seasonal tropical forests and semiarid lands. Molecular work based on mitochondrial and nuclear markers proposed the existence of four haplogroups within P. melanophrys. Peromyscus mekisturus (Puebla deer mouse) was included in one of these haplogroups. We tested the consistency between this hypothesis and external morphology, quantitative and qualitative cranial attributes, and ecological data for a sample of 1,155 specimens spanning the species distribution. We found ecological and morphological consistency with the phylogenetic pattern for P. melanophrys but not for P. mekisturus. We reassessed the taxonomic and nomenclatural status of the populations and type specimens formerly included in P. melanophrys. We concluded that these populations constitute four species: P. zamorae (Zamora deer mouse), distributed in the Mexican Plateau at elevations > 1,500 m; P. micropus (small-footed deer mouse), from lowland tropical deciduous forests of the San Pedro-Mezquital and Lerma-Santiago basins in western Mexico; P. melanophrys (black-eyed deer mouse) from lowland tropical deciduous forests of southeastern Mexico as far as eastern Oaxaca; and P. leucurus (Tehuantepec deer mouse), partially sympatric with P. melanophrys but reaching as far as Chiapas. Data on P. mekisturus were contradictory, and thus was kept as a valid species.