Nucleotide sequences from 94 individuals representing the Oryzomys palustris complex (O. palustris and O. couesi) were examined to assess phylogenetic relationships and taxonomic boundaries. Sequence data from the entire mitochondrial cytochrome-b (Cytb; 1,143 base pairs [bp]), a portion of exon 1 of the nuclear interphotoreceptor retinoid-binding protein (1,266 bp), and intron 2 of the alcohol dehydrogenase 1 (580 bp) genes were analyzed using phylogenetic methods (maximum parsimony and Bayesian inference). In the Cytb analysis, individuals recognized as O. palustris and O. couesi formed reciprocally monophyletic clades supporting their recognition as species; however, additional phylogenetically informative groups were present within each of the 2 nominate clades. In addition, levels of genetic divergence within the currently recognized taxa exceeded values normally associated with intraspecies variation. Together, the phylogenetic and genetic divergence data imply that consideration should be given to recognizing 4 additional species in this complex.