The question of whether epidermolysis bullosa acquisita (EBA) is a distinct entity prompted a review of the Mayo Clinic experience. Twelve patients with this diagnosis were seen from 1955 through 1979, and their records were reviewed. Particular attention was directed to immunofluorescence microscopy (IF), which had been performed in seven patients. Direct IF was positive in seven patients, and indirect IF was positive in four patients. Although many cases of EBA may remain distinct, we believe that the morphologic appearance known as EBA may represent a final common pathway of disease expression in a heterogeneous group of patients with a variety of more specific diseases and that trauma serves as a localizing factor. Our findings indicate that cicatricial pemphigoid probably is the most common specific diagnosis but that all cases of EBA are not represented by this diagnosis. Furthermore, we conclude that when IF is performed, exclusion of other bullous diseases, which is a key criterion for the diagnosis of EBA, is more difficult than previously recognized.