Intrarenal hemodynamic alterations induced by anti-GBM antibody. An isolated perfused kidney system (IPK) was used to study the direct intrarenal hemodynamic effects of binding of anti-glomerular–basement membrane (anti-GBM) antibody in the absence of all other circulating humoral and cellular inflammatory mediators. Control IPK's (perfused with Krebs–Henseleit buffered 5% albumin solution containing nonimmune globulin) had a renal vascular resistance (RVR) mean ± SEM 3.10 ± 0.47 mm Hg/ml/min and a GFR mean ± SEM 0.63 ± 0.8 ml/min/g. Anti-GBM antibody administration raised RVR (4.83 ± 0.52 mm Hg/ml/min, P < 0.01) and lowered GFR (0.34 ± 0.04 ml/min/g, P < 0.01). Perfusate renin activity was higher after antibody administration (684 ± 87 ng AI/ml/hr compared with control 308 ± 42 ngAI/ml/hr, P < 0.01). Treatment with Sar¹Ala⁸All (3 × 10^-6M) or captopril (10 mg/ml) attenuated antibody–induced vasoconstriction (RVR mm Hg/ml/min, Sara¹Ala⁸All = 3.78 ± 0.13 captopril = 3.26 ± 0.12, both P < 0.05 compared with anti-GBM alone). Both inhibitors of the renin-angiotensin system (RAS) also aggrevated the decline in GFR seen after antibody administration (GFR ml/min/g, Sara¹Ala⁸All = 0.24 ± 0.05, Captopril = 0.18 ± 0.03, both P < 0.05 compared with anti-GBM alone). These IPK studies demonstrate that anti-GBM antibody itself may directly induce intrarenal hemodynamic alterations in the absence of complement activation, neutrophil infiltration, neural influences or circulating vasoactive substances. The results from perfusate renin sampling and blockade of the RAS provide evidence that anti-GBM antibody deposition activates the intrarenal RAS and thereby induces significant hemodynamic alterations.