Antibody responses were examined among 998 bighorn sheep (Ovis canadensis) in California (USA) to determine spatial patterns of pathogen exposure. Using a shifting frame analysis, a specific geographic region was delineated that contained bighorn sheep with higher (P < 0.05) levels of multiple exposure (antibodies detected against ≥two pathogens), as well as higher prevalence values for eight of ten individual pathogens. This region in southwestern California encompassed all of the peninsular populations of bighorn sheep recently proposed for listing as endangered by the U.S. Fish and Wildlife Service.