Antiglomerular basement membrane (anti-GBM) diseases-including Goodpasture's (GP) syndrome-and Wegener's granulomatosis (WG) are systemic diseases, which may be diagnosed by means of circulating autoantibodies. Possible overlap syndromes may exist; however, they remain imperfectly defined. We analyzed sera from 31 patients with WG and from 23 patients with anti-GBM disease. All underwent biopsy. Anti-cytoplasmic antibodies (ANCA) were demonstrated by indirect immunofluorescence (IIF); a perinuclear (P-ANCA) or diffuse-cytoplasmic (C-ANCA) staining was discerned. In addition, myeloperoxidase (MPO) antibodies (P-ANCA) and protein 3 (SP3) antibodies (C-ANCA) were analyzed by specific ELISA systems. Anti-GBM antibodies (anti-NC1 antibodies) were detected by ELISA and immunoblotting; the globular domain NC1 of collagen IV was employed as antigen. All 31 WG patients, as defined by clinical and histological criteria, showed ANCA by IIF. Twenty-nine of 31 showed a C-ANCA pattern; all were also positive for SP3 antibodies by ELISA. Three of 31 WG patients were P-ANCA positive by IIF and also had anti-MPO antibodies by ELISA. In one of these patients, SP3 antibodies were additionally found by IIF and by ELISA (double positive). No patient with WG had anti-NC1 antibodies. All 23 serum samples from patients with GP syndrome (N = 19) or anti-GBM glomerulonephritis (N = 4) had anti-NC1 antibodies. In seven of these patients, low titers of anti-MPO antibodies were detected by ELISA; however, the IIF for ANCA was negative. None of these seven patients had extraglomerular vasculities. In addition, the clinical prognosis of these patients was similar to that of those patients who lacked these antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)