Chromosomal change is recognized as an important force in speciation-with-gene-flow models. Although Robertsonian (Rb) translocations contribute to hybrid unfitness and modify recombination patterns, they are generally not considered as efficient as inversions in reducing gene flow. The present study analyses two hybridizing chromosomal races of the house mouse (Mus musculus domesticus), one carrying nine Rb fusions (2n = 22) and the other carrying the ancestral karyotype (2n = 40). Chromosomal heterozygosity involves simple meiotic configurations, the underdominance of which is not as efficient in promoting speciation as more complex chromosomal differences. The pattern of divergence between these races was investigated using 32 microsatellite loci distributed over all autosomes. The results highlighted a relatively large differentiation between the two chromosomal races. The contribution of variation in recombination patterns to this differentiation was supported by the contrasting levels of divergence between proximal vs. non-proximal microsatellite loci. Clinal analyses of the Rb fusions through the hybrid zone uncovered differences in steepness between metacentrics, suggesting associated differences in selection which did not involve linked genic incompatibilities. This study illustrates the significant role of Rb-associated changes in recombination in promoting or maintaining divergence between chromosomal races of the house mouse.