Seventy nephrectomy specimens from patients with end-stage renal disease, four renal biopsies from patients with focal sclerosing glomerulonephropathy (FSGN) and normal renal function, and 17 control biopsies from normal renal allograft donors (Group I) were studied by immunofluorescence with respect to deposition of immunoglobulins and classic and alternative complement (C) pathway components. The end-stage kidneys were divided into three groups according to etiology: 16 patients with immune-mediated glomerulonephritis (Group II), 22 patients with congenital and/or familial renal disease (Group III), and 32 patients with systemic or primary renal disease in which an immune-mediated injury could not be established (Group IV). The pattern of immunoprotein deposition in glomeruli in Groups II, III, and IV, and in biopsies of patients with FSGN was similar: peripheral lobular, globular and/or granular, focal and segmental; it was limited to dying glomeruli or abnormal glomerular segments. A statistically significant correlation existed between the percent of properdin-containing glomeruli and the percent of glomeruli undergoing hyalinization in Groups II, III and IV (II, r=0.67; III, r=0.92; IV, r=0.78). No deposition was observed in normal or completely fibrotic glomeruli. In vitro heterologous complement fixation was demonstrated in 17/19 end-stage kidneys in a similar distribution. Early classic C components, C1q and C4, were detected in a somewhat higher frequency in Group II (14/16) than Group III (11/22) and Group IV (20/32) (Group II vs. III, P=.02 and II vs. IV, P=.07). C3 and properdin were detected in 77 to 100% of all 3 groups; in 18 patients, C3 and properdin were present without detectable C1q and C4. Immunoglobulins, primarily IgM, and components of the classic and alternative C pathways are regularly present in hyalinizing glomeruli irrespective of the etiology of the renal failure. These observations suggest that an immune process is operative in glomerular obsolescence regardless of the underlying etiology of the renal disease.