A patient with severe cicatricial pemphigoid demonstrated both in vivo bound and circulating anti-basement membrane zone antibodies of the IgA and IgG classes. Complement component 3(C3) was also deposited in the basement membrane zone of lesional skin as well as in normal-appearing buccal mucosa of the patient. However, C1q was absent, while granular deposits of two factors of the alternative complement activating pathway, properdin and properdin factor B, were present only in the basement membrane zone of lesional skin, but not in normal buccal mucosa. Deposition of alternative complement pathway reactants in the lesion suggests that complement activation by IgA was associated with lesion development. Western blot analysis of the patient''s serum on electrophoresed cultured keratinocyte antigens identified two distinct sets of epidermal antigens. While IgG bound antigens of 230, 205, 140, and 90kd, the patient''s IgA antibodies bound a distinct set of antigens, 180 and 130 kd. The potential pathogenic role of IgA in cicatricial pemphigoid is discussed.