Fc-specific reticulo-endothelial (R-E) clearance was determined in control subjects (n = 11) and in patients with immune complex (IC) glomerulonephritis (n = 22) and systemic lupus erythematosus (SLE) nephritis (n = 10). Clearance (t1/2) depended on the removal of autologous erythrocytes labeled with 51chromium and sensitized with anti-D IgG by fixed splenic macrophages bearing receptors for the Fc portion of the IgG molecule. A significant difference in clearance rates was demonstrated between normal individuals with and without the HLA-B8, DR3 haplotype. Marked clearance defects were found in SLE (8/10), and t1/2 correlated with the levels of circulating IC. Delayed clearance was also observed in 6/11 patients with IgA nephropathy or Henoch-Schönlein purpura and in 4/11 patients with membranous nephropathy (MN). No correlation was found between circulating IC levels and t1/2 in these diseases. Clearance defects in these patients did not correlate with the presence of the HLA-B8, DR3 haplotype. This study demonstrates that some patients with IC glomerulonephritis have defective Fc-mediated clearance that does not appear to be secondary to IC blockade.