Fogo selvagem (FS), the endemic form of pemphigus foliaceus (PF), is an autoimmune blistering disease characterized by autoantibodies against desmoglein 1. The Terena reservation of Limao Verde in Mato Grosso do Sul, Brazil, is a previously identified focus of disease. Autoantibodies against desmoglein 3 (Dsg3) have also been detected in sera from patients with FS. In an effort to further characterize the serological, geographical, and clinical epidemiology of the disease, we sought to determine the prevalence of anti-Dsg3 autoantibodies in sera from normal subjects living outside of and in an endemic area using an ELISA. Anti-Dsg3 antibodies were detected in 53 of 146 normal subjects from Limao Verde (36%), and in eight of 140 normal subjects from surrounding areas (6%). A significant trend was observed in the proportion of positive tests relative to distance from the endemic area (P<0.001). Our seroepidemiological observations support the concept that the likely environmental trigger of the antibody response in FS is located in this endemic area, and that the population at risk to develop FS may also be at risk to develop an endemic form of pemphigus vulgaris as reported by our co-investigators from Brasilia. © 2006 The Society for Investigative Dermatology.