Fractions of IgG from sera of patients with pemphigoid and pemphigus added to monolayer cultures of mouse epidermal cells resulted in a sparse distribution of cells. Direct immunofluorescence studies of these monolayers revealed epidermal cell surface antigens reacting with pemphigoid and pemphigus antibodies. We suggest that these antibodies may bind to epidermal cell surface antigenic molecules which are important in maintaining epidermal cell adhesion in culture.