Bullous pemphigoid (BP)-type autoantibodies were found by Western blot (WB) analysis of epidermal extracts in the serum of 38% of HIV-seropositive patients compared with 21 % of HIV-seronegative patients with chronic pruritus and 76% of patients with BP. They were further identified as BP autoantibodies (BPab) by immunoprecipitation and immunoelectron microscopy. Their incidence increased from 21% in HIV infection stage II to 37% and 43% in stages III and IV, respectively. Of the patients suffering from HIV-related chronic pruritic papulovesicular eruption, 75% showed circulating BPab as compared with 29% in those without skin problems (P= 0.0066) and, among them, 30% met the diagnostic criteria for BP when histology, WB, immunofluorescence and immunoelectron microscopy techniques were used. In conclusion, this study identifies an autoimmune skin reaction that may account for, or be related to, the distressing pruritic eruptions occurring in HIV-infected patients.