The serum of a 34-year-old woman with the Hallopeau type of pemphigus vegetans (PVg) contained antibodies against a 130-kDa polypeptide in human epidermal lysates, as revealed by Western blot analysis. The serum strongly fixed complement in vitro, and the PVg lesional skin contained a predominance of complement-fixing IgG2 and IgG4. Although the antigens reactive with sera from PVg and pemphigus vulgaris were the same, strong fixation of complement by PVg antibodies, due to the presence of complement-dependent IgG subclasses, and subsequent in situ activation of complement, might explain the marked infiltration of neutrophils and eosinophils in PVg.