Seven rabbits were studied after immunization with human plasma fibronectin which had been purified by preparative sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis run after reduction. Light- and electron-microscopic examination of kidneys revealed proliferative mesangial and capillary alterations in all of the rabbits immunized with fibronectin, but not in the rabbits immunized with fibrinogen or saline. In addition, one of the rabbits (Rabbit 4) also demonstrated dense deposits in a unique distribution within the glomerular basement membrane. Granular staining for rabbit IgG was present in the mesangium and along the basement membranes of the capillary loops of glomeruli from Rabbit 4 as detected by immunohistochemical methods. Sera from all of the rabbits immunized with human fibronectin contained IgG antibodies that reacted with rabbit fibronectin when tested by the Western blotting method. Preimmune sera and sera from rabbits immunized with fibrinogen or saline recognized neither human nor rabbit fibronectin. Although antibodies from several of the rabbits reacted with the 27,000-dalton, aminoterminal fragments of human fibronectin by the Western blotting method, only antibodies from Rabbit 4 recognized the 27,000-dalton fragment of rabbit fibronectin. These studies indicate that antibodies which recognize fibronectin of the host species and which are involved in the pathogenesis of glomerular injury can be induced by immunization with denatured heterologous fibronectin monomer.