The tribe Phyllotini is an advanced group of 46 endemic species among the Muridae of South America, that being adapted to its xeric environments, seems to have the Southern Altiplano as its original differentiation area (Reig 1986). This hypothesis is tested by examining the geographic distributions and cytogenetic data from 35 species, including the Andinomys edax and Euneomys chichilloides G band descriptions: its comparison with Phyllotis, AgNOR bands and rDNA FISH in seven species, as well as protein electrophoresis data (118 electro-alleles in 12 species) and cytochrome b gen sequences in the mtDNA (407 bp in 14 species). All karyotypes were chromosomically different, except in two cases with unknown G bands. A general association between altiplanic distribution of species with ancestral character states (telocentric chromosomes, high 2n, basal positions in phylogenies based on protein and cytochrome b gene sequences) was found, as well as between non-altiplanic distribution with derived states. Different combinations of Altdinomys-like chromosomal arms that would have suffer ed centric fusions to form the metacentric chromosomes of Euneomys and Phyllotis, respectively, are documented here, and also a reduction of the number of structural NOR in Auliscomys compared to Loxodontomys, all derived features showing a diversification to the south and another to the north respectively, from a center in the southern Altiplano.