The purpose of this research is to investigate the immunopathogenesis of bullous pemphigoid using an in vitro model which simulates many of the immunological and histological features of the disease. The model consists of cryostat sections of normal human skin as a source of pemphigoid antigen, sera from patients as a source of anti-basement membrane zone antibody, fresh serum complement and peripheral blood leukocytes. When incubated together, antibody and complement bind to the dermalepidermal junction and leukocytes migrate by chemotaxis and attach to the junction. The leukocyte activity is antibody and complement dependent representing the first functional assay for pemphigoid antibody mediated complement activation. Incubation of skin with attached leukocytes for 90-180 minutes results in dermal-epidermal separation histologically identical to that observed in vivo. The specific objectives of the study are to: 1) using leukocyte attachment at the dermal-epidermal junction as a functional assay for complement activation, define the pathway(s) of pemphigoid antibody dependent complement activation and the role of complement components in the chemotaxis and attachment of leukocytes to the dermal-epidermal junction, 2) using immunoflourescence, electromicroscopy, immunoferritin electronmicroscopy and ultrastructural histochemistry, study the leukocyte functions occurring at the dermal-epidermal junction including phagocytosis, degranulation and discharge of lysosomal enzymes and 3) using routine light and electronmicroscopy, determine the sequence of structural changes caused by leukocytes in vitro and compare these to changes reported in patients skin and to changes reported in a prospective study of the ultrastructural changes in lesions from patients at this institution.