Background: The research on endemic pemphigus foliaceus (fogo selvagem) has mainly focused on the humoral immune response, but little attention has been given to the function of cell-mediated immune response and the nature of the cellular elements of the tissue reaction in the lesions of fogo selvagem. Objective: The purpose of this study was the immunophenotype characterization of the inflammatory cells as well as the expression of adhesion molecules and HLA-DR in the perilesional and lesional skin of fogo selvagem. Methods: Twenty biopsy specimens of lesional and perilesional skin were analyzed by immunohistochemical techniques. The panel of monoclonal antibodies consisted of CD8, CD4, CD1a, HLA-DR, IL-2R, LFA-1, ICAM-1, and PAN-B. Results: The semiquantitative analysis of the cell population revealed a predominance of CD4 T lymphocytes in the tissue response of perilesional and lesional skin. The population of epidermal Langerhans cells was decreased in lesional skin when compared with the perilesional skin, whereas CD1a⁺ dermal dendritic cells predominated in lesional skin. Keratinocyte expression of ICAM-1 and HLA-DR was negative in both lesional and perilesional skin. Conclusion: The overall results suggest the participation of the cell-mediated immunity in endemic pemphigus foliaceus (fogo selvagem). The lack of keratinocyte ICAM-1 expression may be related to the pattern of cytokines secreted by the CD4⁺ T cells of the tissue reaction in fogo selvagem. (J Am Acad Dermatol 2001;44:446-50.)