To investigate the heterogeneity of epitopes recognized by anti-GBM autoantibodies in sera from a large cohort of Chinese patients with anti-GBM disease and its clinical significance.The present study included 108 patients with anti-GBM disease who were diagnosed in our hospital, between Jan 1991 and May 2009, with complete clinical and renal pathological data. Sera or plasma exchange of the patients were used to incubate with cryostat section of normal human renal tissue for indirect immunofluorescence (IIF) assay. The cryostat sections of normal renal tissue were pre-treated by 6 mol/L urea to unmask cryptic epitopes, and untreated cryostat sections were used to detect natural exposed epitopes. The sera were diluted from 1:2 to 1:512 to determine titers of anti-GBM autoantibodies Patients with anti-GBM autoantibodies against cryptic or exposed epitopes were further stratified; their clinical and pathological associations were analyzed.Sera from all the 108 patients could recognize cryptic epitopes on normal renal tissue (urea treated section). IIF showed IgG linear staining along GBM. However, sera from 56/108 patients (group A) could also recognize exposed epitopes on normal renal tissue (untreated section); sera from the rest 52/108 patients (group B) could not recognize exposed epitopes. In urea treated condition, the average titer of anti-GBM autoantibodies from sera of patients in group A was significantly higher than that in group B (P<0.01), ANCA-positive patients in group A were significant less than that in group B (P<0.01). There was no significant difference between the two groups in regard to other clinical data (including serum creatinine) and renal histopathologic data.Anti-GBM autoantibodies from some patients with anti-GBM disease could recognize natural exposed epitopes, however, their anti-GBM titer for cryptic epitopes was higher than that of those recognizing cryptic epitopes only and the prevalence of serum ANCA was significantly less.