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In this study I provide a phylogenetic hypothesis for the tribe Oryzomyini that can be used to understand the diversification and evolution of this group of rodents and to revise the current generic-level classification. Morphological and molecular data were used for these purposes in combined and separate analyses. Molecular data consisted of partial sequences (1266 bp) from the first exon of the nuclear gene encoding the interphotoreceptor retinoid binding protein (IRBP); the morphological matrix comprised 99 characters, including 16 integumental characters, 32 skull characters, 29 dental characters, 7 postcranial characters, and 10 characters from the phallus and soft-anatomy systems. I present anatomical descriptions for each character, including delineation of different states observed among oryzomyines. Results of the combined analysis were congruent with the IRBP-only dataset for oryzomyine higher-level relationships. Morphological analyses, although showing discrepancies from the combined or IRBP consensus cladograms and with low nodal support values, recovered several clades similar to the combined and IRBP analyses. Systematics of the tribe and the evolution of a few pivotal characters are discussed in light of the proposed phylogeny. Different taxonomic arrangements for species currently included in the genus Oryzomys are suggested. Finally, I evaluate evolutionary and biogeographic hypotheses that are compatible with our current knowledge on oryzomyine relationships.