An enzootic focus of rabies in skunks in Mexico is described. Fifty three wild animals including two badgers (Taxidea taxus), 32 bats (various species), one bobcat (Lynx rufus), two coatis (Nasua narica) three foxes (Urocyon cineroargenteus), one raccoon (Procyon lotor) and 12 skunks (see below) were tested for rabies by direct immunofluorescence assay from 1991 to 1997 in the central part of San Luis Potosi State, Mexico. Rabies occurrence was 21% of all tested mammals, with 19% in skunks and only 2% in other wild species (one bobcat). Skunks represented 23% of all mammals tested and had a rabies prevalence of 83%. Only 10 individuals were identified: three hog-nosed skunks (Conepatus leuconotus) and seven spotted skunks (Spilogale putorius). All were involved in human attacks; the spotted skunk attacks were inside bedrooms while people were sleeping, and the hog-nosed skunk attacks occurred outdoors. Skunk cases of rabies represented 40% of all rabies cases in 1997, and 100% of cases registered for wild animals in San Luis Potosi state. This situation constitutes an important public health problem and requires further epidemiological research to make the human population aware of the problem and to establish measures to limit further human attacks by rabid skunks.