Epizootiological patterns of rabies are described, using antigenic and genetic analysis of samples obtained from infected domestic and wild mammals in 20 Mexican states during 1976-2002. Two independent origins are suggested for rabies in Mexican carnivores. One group shares ancestry with canine rabies, while the other group appears to share a common origin with bat rabies in North America. More than 12 sublineages were found in rabid dog populations, suggesting at least six major spatio-temporal foci. Coyote rabies was found as independent enzootic foci that probably emerged via spillover from dog rabies, translocated from major foci in the southcentral and western regions of Mexico. One focus of gray fox rabies was widely distributed in northwestern Mexico, overlapping with a focus in the same species in the southwestern United States. A skunk rabies focus distributed in the northcentral Mexican states appears to share a common origin with bat rabies foci in North America, and is a close relative of southcentral skunk and raccoon rabies in the United States. Two other skunk foci share a common ancestor with canine rabies and were distributed in northwest Mexico and Yucatan.