Anti-basement membrane antibodies are now being associated with an increasing spectrum of disease, including Goodpasture's syndrome, rapidly progressive and occasionally milder forms of glomerulonephritis (GN), tubulointerstitial nephritis, pulmonary damage, and potentially other forms of tissue injury. We have developed a radioimmunoassay to detect circulating antiglomerular basement membrane (GBM) antibodies. The antigens for this assay are derived from the noncollagenous portion of the GBM remaining after collagenase digestion. After immunoabsorptive purification, the major antigens precipitated by human anti-GBM antibodies can be characterized by polyacrylamide gel electrophoresis (PAGE) into an unresolved high molecular weight fraction and two antigenic peaks of 54,000 and 27,000 daltons. The noncollagenous nature of the antigenic material has been confirmed by amino acid analysis. The radiolabelled antigen has proven useful in detecting circulating anti-GBM antibodies in over 500 patients. The assay is of use in monitoring the activity of disease and judging the patient's response to therapy. It is also useful in determining the timing of renal transplantation, if required. Differences in antigenic content of glomerular and tubular basement membranes (TBM) have been noted between individuals. These antigenic differences, under certain circumstances, can lead to the induction of anti-basement membrane antibody responses after transplantation.