Background Endemic pemphigus foliaceus (EPF) is an organ-specific blistering disease of the epidermis characterized by the presence of IgG autoantibodies, specifically desmoglein (Dsg)1. This condition has been reported particularly in Brazil, Colombia, Tunisia and Peru. Aim To characterize the humoral response against Dsg1 and Dsg3 autoantibodies of patients with EPF from the Peruvian Amazon region. Methods Blood samples were collected from 16 patients with a clinical diagnosis of EPF, and tested using indirect immunofluorescence (IIF), immunoprecipitation and ELISA (for IgG and its subclasses against Dsg1 and IgG against Dsg3). Results Autoantibodies against the intercellular spaces were detected by IIF in 82.5% and 87.5% of patients, using normal human skin and monkey oesophagus, respectively. Sera from all patients immunoprecipitated recombinant Dsg1, and three serum samples immunoprecipitated recombinant Dsg3 (6.25%). Using ELISA, anti-Dsg1 antibodies were detected in 13 patients (81.25%), and both IgG1 and IgG2 antibodies against Dsg1 in 12 patients (75%). All patients were positive for IgG4 autoantibodies, and only one patient was positive for IgG3 autoantibodies (6.25%). Anti-Dsg3 antibodies were detected in five patients (31.25%). Conclusions EPF from Peru shares epidemiological, clinical and immunological characteristics with other forms of EPF that have been described in South America.