Fixation of centric fusions in natural populations often encounters minimal meiotic problems due to the ability of trivalents to segregate normally; therefore, little sterility barrier is achieved between a founder population and the parental stock. However, a strong sterility barrier can develop between different founder populations fixed for centric fusions that are monobrachially homologous in the resulting biarmed chromosomes (one arm is homologous but the other is nonhomologous). Hybridization through secondary contact then results in complex multivalents, which encounter problems in segregation and produce unbalanced gametes. Speciation mediated by centric fusions is a peripatric speciation model that does not postulate populational phenomena atypical of those characteristic of most mammals. The model appears applicable to a diversity of mammalian taxa such as bats of the Rhogeessa tumida-parvula complex, shrews of the Sorex araneus complex, and rodents of the Mus musculus and Rattus rattus complexes.