The effect of cyclosporin A (C YA) on the development of active and passive modeis of rat anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM-GN) was assessed. Active GN was induced by an intravenous injection of sheep anti-rat GBM globulin to preimmunized rats. After 5 days, a diffuse proliferative GN with proteinuria and linear GBM deposition of rat IgG was regularly observed. CYA treatment, commencing prior to preimmunization, significantly attenuated the glomerular lesion, reduced proteinuria, prevented linear deposition of rat IgG and reduced the serum titre of anti-sheep globulin antibody. However, treatment started after the antibody response was established failed to alter antibody production, its glomerular deposition or the outcome of the disease. CYA treatment did not effect passive anti-GBM-GN, occurring 24 h after intravenous administration of sheep anti-rat GBM globulin to unimmunized rats. Thus, CYA is able to block anti-GBM-GN when given prior to induction of disease, by preventing an active antibody response. However, it did not alter GN when the antibody response was well established, or when glomerular injury was passively induced.