The goal of this project is to study the relationship between genetic polymorphism of the third component of complement (C3) and human glomerulonephritis. Our preliminary studies reveal that genetically controlled hypocomplementemia occurs in some family members of patients with glomerulonephritis, partial lipodystrophy, vasculitis and lupus-like disease. C3 polymorphism is evaluated by prolonged agarose electrophoresis and spectrodensitometry of stained plates. Hypocomplementemic sera are typed with the help of immunofixation and radio-immunofixation . We have detected a significant increase in C3 Fast gene in membranoproliferative glomerulonephritis (X2 equals 9.29, p is less than .02) and an increased incidence of hypomorphic C3 Fast in patients with glomerulonephritis. The biologic significance of increased C3 Fast and hypomorphic C3 Fast is now known but may be related to mediation of cytolysis or C3 receptor activity.