Anti-glomerular basement membrane (GBM) glomerulonephritis, which was among the earliest recognized human autoimmune diseases, is characterized by the presence of anti- -GBM antibody. It has been a prototypical example of autoantibody-mediated autoimmune disease. However, decades of research on this disease, based either on clinical observations or experimental models, have revealed that T cell-mediated cellular immunity may potentially be a more important mediator of glomerulonephritis. We have made several breakthroughs in understanding the T cell-mediated mechanism causing this disease in a rat model based on Goodpasture's antigen, non-collagen domain 1 of ?3 chain of type IV collagen (Col4alpha3NC1). We demonstrated that anti-GBM glomerulonephritis was induced by either passive transfer of Col4alpah3NC1-specific T cells or active immunization with the nephritogenic T cell epitope of Col4alpha3NC1. Immunization with the T cell epitope also triggered production of anti-GBM antibodies to diversified GBM antigens. Thus, a single nephritogenic T cell epitope alone is sufficient to induce the clinical spectrum of anti-GBM glomerulonephritis, including proteinuria, glomerular injury, and anti-GBM antibody. A possible T cell-mediated mechanism for causing human anti-GBM disease is proposed.