Random bred Swiss-Webster mice were immunized with either autologous (MFN) or heterologous guinea pig (GPFN) denatured serum fibronectin. Immunofluorescent, light, and electron microscopic examination of renal tissues demonstrated glomerular changes, consisting primarily of endothelial and mesangial cell hypertrophy with expansion of the mesangial matrix. Evagination of mesangial cytoplasm into capillary lumens and balloon-like structures were characteristic of affected glomeruli. The histopathologic alterations were present in varying degrees of severity in all fibronectin treated animals, with slightly more extensive glomerular proliferation seen in animals immunized with heterologous (GPFN) fibronectin as compared to mice immunized with autologous (MFN) protein. Perivascular mononuclear cell infiltration with edematous changes in medial smooth muscle cells occured in renal vessels. The vasculature of the liver and lung also showed mononuclear cell infiltrates in the adventitia. These studies lead us to conclude that an immune response to either heterologous or autologous denatured serum fibronectin can induce glomerular sclerotic changes, cellular hyperplasia, and vascular injury. © 1982 Springer-Verlag.