Spiny mice of the genus Acomys traditionally have been classified as members of the Murinae, a subfamily of rodents that also includes rats and mice with which spiny mice share a complex set of morphological characters, including a unique molar pattern. The origin and evolution of this molar pattern, documented by many fossils from Southern Asia, support the hypothesis of the monophyly of Acomys and all other Murinae. This view has been challenged by immunological studies that have suggested that Acomys is as distantly related to mice (Mus) as are other subfamilies (e.g., hamsters: Cricetinae) of the muroid rodents. We present molecular evidence derived from DNA.DNA hybridization data that indicate that the spiny mouse Acomys and two African genera of Murinae, Uranomys and Lophuromys, constitute a monophyletic clade, a view that was recently suggested on the basis of dental characters. However, our DNA.DNA hybridization data also indicate that the spiny mice (Acomys) are more closely related to gerbils (Gerbillinae) than to the true mice and rats (Murinae) with which they have been classified. Because Acomys and the brush-furred mice Uranomys and Lophuromys share no derived morphological characters with the Gerbillinae, their murine morphology must have evolved by convergence, including the molar pattern previously considered to support the monophyly of the Murinae.