Recent findings indicate that the pemphigus foliaceus (PF) antigen is involved in epidermal cell adhesion and that characteristic PP lesions result from loss of this function as a consequence of autoantibody binding. In the present communication we present data on the epitopes involved in the human autoantibody binding to an immunologically reactive murine tryptic fragment of the PF antigen (tf-PF). Immunoprecipitation experiments showed that 39 PF sera, obtained from North American, Colombian, and Brazilian patients recognized only calcium-sensitive epitope(s) on the tf-PF. Immunofluorescence blocking experiments showed that preincubation with tf-PF completely blocked the immunofluorescence of 80% of the sera when tested on human skin substrate, and 86% of the sera when tested on murine skin substrate. These results show that the calcium-sensitive epi- tope(s) originally recognized on human PF complex, is (are) present on the murine tf-PP and constitute(s) a major antigenic region for the human PF autoantibodies. They also implicate this region of the PF antigen in the pathogenesis of PF as well as in epidermal cell adhesion.