The demonstration of circulating anti-glomerular basement membrane (GBM) antibodies is almost diagnostic for anti-GBM disease and Goodpasture's syndrome. These antibodies are, however, occasionally present in SLE and diabetes, in association with IgA disease and membranous nephropathy and after transplantation in Alport's syndrome. In addition, we describe circulating anti-GBM antibodies in a research worker who handled GBM and in whom coeliec disease later developed, and in an individual with epidermolysis bullosa acquisita. Neither patient had impaired renal function nor an abnormal urinary sediment, suggesting either that these antibodies were of low affinity, or that additional factors are required for the pathogenesis of an aggressive glomerular lesion when circulating anti-GBM antibodies are present. In at least one of these individuals anti-GBM antibodies may have developed after the exposure of basement membrane collagen type IV to activated immunological mediators and cells.