Damage to glomerular endothelial cells, which are the constituents of the size-dependent and charge-dependent glomerular barrier, may result in proteinuria. Brain endothelial cell plasma membrane possesses an intrinsic potential antigenicity which is capable of injuring the blood-brain barrier and causing widespread demyelination in the brain. To examine the pathogenetic effect on the glomerulus of plasma membrane sensitization, we injected guinea pigs with a single dose of plasma membrane products derived from cultured endothelial cells from the brain and umbilical cord, and observed the resulting effects both clinically and by histological, immunofluorescence and ultrastructural examinations of renal tissues. The animals immunized with plasma membrane products showed clinically mild proteinuria. Proliferative changes in the mesangial matrix with mild mononuclear cell infiltration was observed in the glomeruli of all experimental animals. Immunofluorescence studies showed finely granular, peripheral capillary loop and mesangial staining for IgG and C3. Electron microscopy revealed fine, electron-dense deposits in the subendothelial region. In addition, titers of anti-endothelial cell antibodies and circulating immune complexes were significantly high. It was suggested that antibody-mediated immune mechanisms might play a role in the pathogenesis of this glomerular tissue injury induced by immunization with cultured endothelial cell plasma membrane products.