The chromosomal phylogeny of the African genus Mastomys was undertaken to clarify their taxonomic position and to estimate the relevance of chromosomal evolution in the diversification of this genus. Four species of Mastomys (M. erythroleucus, M. huberti, M. natalensis, and M. coucha) were compared to closely related African rats, Myomys daltoni and Praomys tullbergi, and to three species of European murids. The phylogenetic trees generated could be grouped into two topologies in which Mastomys was either monophyletic or paraphyletic. A cladistic and phenetic analysis of available allozymic data clearly showed, however, that Mastomys species form a closely related group and agreed with a monophyletic origin for this genus. Chromosomal evolution in Mastomys is characterized by seven different types of rearrangements, the most frequent being pericentric inversions. The latter also are involved in intraspecific, chromosomal polymorphisms suggesting that pericentric inversions are a recurrent event in the evolution of this genus. However, pericentric inversions modify the fundamental number, but not the diploid number, which is a criterion often used to identify the different species of Mastomys. These observations suggest the following pattern of chromosomal change in this genus. Rearrangements modifying the diploid number occurred at the same time as major speciation events resulting in different diploid numbers for each species whereas subsequent divergence of karyotypes proceeded mainly by accumulation of pericentric inversions.