Oryzomys megacephalus (Fischer, 1814) is the oldest available name based on Azara’s (1801) "Rat second, ou Rat a grosse tete," a form conventionally known as O. capito (Olfers, 1818) in the middle 1900s (e.g., Cabrera, 1961; Hall, 1981; Hershkovitz, 1960). Taxonomic understanding of this species was obscured by the infelicitous footnote of Hershkovitz (1960:544), who suggested the synonymy of some 20 taxa under O. capito, a passing opinion formally expanded by Cabrera (1961) and followed by other authors (e.g., Hall, 1981; Handley, 1966a, 1976). The extremeness of this viewpoint was exposed by the karyotypic study of Gardner and Patton (1976), a watershed paper that has sparked critical review, still on-going, of this diverse species complex.
As a result, the following forms considered synonyms by Hershkovitz (1960) and/or Cabrera (1961) are now acknowledged as distinct species or as synonyms of other species (see separate accounts): O. bolivaris, boliviae (= O. nitidus), castaneus (= O. bolivaris), O. caracolus, intermedius (= O. russatus), O. laticeps, O. legatus, magdalenae (= O. talamancae), O. macconnelli, medius (= O. talamancae), mollipilosus (= O. talamancae), O. nitidus, oniscus (= O. laticeps), O. perenensis, rivularis (= O. bolivaris), sylvaticus (= O. talamancae), O. talamancae, and O. yunganus. Nomenclatural priority, neotype designation, synonyms, and morphological definition of O. megacephalus proper addressed by Musser et al. (1998); phylogeographic relationships and other morphometric comparisons supplied by Patton et al. (2000); banded chromosomal comparisons with related species presented by Volobouev and Aniskin (2000). Sister species to O. laticeps (Bonvicino and Martins Moreira, 2001; Costa, 2003) or the O. laticeps O. perenensis clade (Patton et al., 2000) based on cytochrome b sequence data.