The most important reservoir of wildlife rabies on the American Great Plains is the striped skunk. A rabid striped skunk taken in August 1988 near Deaver, WY became the index case for a subsequent epizootic in a previously skunk rabies free area. In 1989, more rabid skunks occurred and the epizootic was moving throughout Sage Creek and in later years (1990-1993) through the entire Shoshone River basin. Federal, state, and local officials cooperated in a rabies program with the goal of addressing the health and safety of the region’s citizens, domestic animals, and livestock. Three areas of focus in the program were: 1) immunization of pets and livestock, 2) public education, and 3) skunk population monitoring and control. Rabies immunizations were re-emphasized by the local veterinarians and public health officials for pets to decrease potential rabies spillover to other species. Public education emphasized the dangers of rabies and the behavior of rabid animals using local news media and assemblies at area schools. This paper provides a synoptic overview of the third component – skunk population monitoring and control provided by USDA/APHIS’s Wyoming Wildlife Services (WS). WS provided trapping expertise starting in 1990 with rabid specimens identified by the Wyoming State Veterinary Laboratory. Starting in 1990, WS’s National Wildlife Research Center provided data analysis of rabid locations for the entire epizootic (i.e., 1988-1993). These analyses demonstrated the epizootic’s movements through the novel first use of a Geographic Information System that merged a wildlife disease (i.e., rabies) case/capture locations and dates with additional GIS data layers including hydrology, human population density, and land use. The epizootic ended in 1994 with striped skunks, bats, cats, and one horse affected. Studying this epizootic should benefit officials in planning future surveillance and/or depopulation programs. This study demonstrated the need for a skunk rabies vaccine and effective delivery system, and if the latter had been available maybe this epizootic would have been more limited in its scope and duration.