We have studied various tissues from 10 patients with cicatricial pemphigoid using direct and indirect immunofluorescence, mechanical suction blister induction, and immunoelectron microscopy. In 8 of the 10 patients, direct immunofluorescence of buccal mucosa showed a linear deposition of immunoreactants, IgG and C3 being those most commonly detected. Direct immunofluorescence of skin was positive in only 4 patients. Only 1 patient had a detectable circulating anti-basement membrane zone antibody. Substitution of normal human oral mucosa for adult skin as the tissue substrate for indirect immunofluorescence did not prove useful in the detection of circulating autoantibodies. Immunoelectron microscopy was performed in the skin or mucosa (buccal or ocular) of 6 patients, revealing lamina lucida localization of in vivo-bound immunoreactants. Indirect immunofluorescence studies on mechanically induced suction blisters in skin of 2 patients with in vivo-bound IgG suggest that the lamina lucida antigen involved in cicatricial pemphigoid may be distinct from the bullous pemphigoid antigen.