The glomerular fixation of anti-glomerular-basement-membrane (antiGBM) antibody is associated with complement activation, neutrophil accumulation, and renal injury. This injury manifests both as an increase in the rate of urinary protein excretion and altered renal hemodynamic characteristics. We have utilized an isolated perfused kidney system (IPK) to assess the capacity of antiGBM antibody to alter glomerular permselectivity in the absence of both glomerular complement activation and neutrophil infiltration. Control perfusions with Krebs-Henseleit buffered 5% albumin solutions containing normal sheep globulin had a protein excretion rate of 0.223 +/- 0.044 mg/min (mean +/- SEM). Assessment of glomerular permselectivity using fractional dextran clearances demonstrated an intact negative charge barrier in control preparations. AntiGBM antibody bound in a dose related fashion to the kidney and was localized to the glomerular basement membrane on immunofluorescence. Antibody induced a significant increase in mean protein excretion (2.009 +/- 0.681 mg/min, P less than 0.01) in association with a loss of the glomerular filter's negative charge barrier. These IPK studies demonstrate that antiGBM antibody can itself produce proteinuria, in association with loss of the glomerular capillary negative charge barrier, in the absence of all circulating humoral and cellular inflammatory mediator systems.