We have previously generated a monoclonal anti-idiotypic antibody (antiId 3-17) specific for a cross-reactive idiotype (CRI) present in sera and bound at the basement membrane zone (BMZ) in some patients with bullous pemphigoid (BP). The purpose of the present study was to determine if CRI isolated from sera of patients with BP expressed anti-BMZ activity. CRI, isolated by affinity chromatography from 5 nonrelated patients with BP, bound to the epidermal side of normal human split skin as detected by indirect immunofluorescence. In patients with BP, the presence of the CRI on circulating IgG is associated with anti-BMZ activity.