The association among different morphotypes and locomotor types and habitat preference has been repeatedly mentioned in the sigmodontine literature; however, those associations have been seldom tested. The goal of the present study was to morphologically characterize and compare sigmodontines from Venezuelan Guayana in relation to their type of locomotion and habitat. Specimens belonging to 13 genera were classified on the basis of locomotion (terrestrial, climbing-arboreal, and semiaquatic) and habitat preference (forest and open areas). Ten body measurements were recorded and features of the ears, fore- and hindfoot, rostral vibrissae, and tail scales were scored. A principal component analysis distinguishes three groups: A) one composed of terrestrial forms from open areas (Necromys, Sigmodon, Zygodontomys, and Calomys); B) another form by semiaquatic genera (Neusticomys, Holochilus, and Nectomys); and C) the last one form by genera from forested areas plus Oligoryzomys. A cluster analysis defines two main groups: one formed by groups A (except Calomys) and B (except Neusticomys) and the other containing Calomys, Neusticomys, and the group C that in turns is subdivided into a subgroup of terrestrial forms and a subgroup of climbing-arboreal forms. Taken as a whole our results show that genera from a particular habitat are more similar to each other than to genera from other areas or those that posses a different locomotion type. Members of each of these three groups are not more closely related among them than to members of other groups. Therefore, inferring sigmodontine phylogenetic relationships from external characters should be undertaken with caution. © SAREM, 2010.