Bullous pemphigoid (BP) is the most common autoimmune bullous disease of the elderly and is associated with IgG and IgE autoantibodies against the hemidesmosomal proteins, BP180 and BP230. The purpose of this study was to characterize the epitope specificity of IgE against defined regions of BP180 and BP230 in 32 BP patients and 21 elderly patients with pruritic disorders who did not yet fulfill all the criteria of BP by immunoblot (IB), ELISA and indirect immunofluorescence microscopy. Our findings show that IgE from BP sera preferentially targets the COOH-terminus of BP230 (IB: 16/32, ELISA: 12/32) and, to a lesser extent, the BP180-NC16A domain (IB: 11/32, ELISA: 9/32). Noteworthy, a subgroup of elderly patients with pruritic dermatoses also showed IgE recognition of BP180-NC16A (IB: 1/21, ELISA: 4/21) and less frequently of BP230 (IB: 2/21, ELISA: 2/21). Thus, IgE recognition of the BP autoantigens is presumably an early pathogenetic event in BP.