Seven perilesional skin samples which appeared to be normal were obtained from patients with pemphigus and studied by means of direct immunofluorescence and horseradish peroxidase labeled antibody methods. Light microscopic observations revealed that in vivo bound IgG and C3 were localized in the intercellular cement substance region of the epidermis in both the direct immunofluorescence and horseradish peroxidase labeled antibody method in exactly the same fashion. Immunoelectronmicroscopic observations revealed that bound IgG and C3 were localized exclusively in the epidermal intercellular cement substance region, but not in any intracellular organellae, pinocytotic vesicles, cytosol, basal lamina or upper dermis. Bound IgG was detected in all seven cases. Bound C3 was detected in four of the seven cases. Both of these globulins were localized exclusively in the nondesmosomal and desmosomal epidermal intercellular cement substance region, apparently in the same fashion. It was suggested immunoelectronmicroscopically that not only IgG, but also the complement system might be involved in the formation of the skin lesion in pemphigus.