To determine whether patients with systemic lupus erythematosus and nephritis have profound defects in mononuclear phagocyte system clearance than their counterparts without renal disease, we studied Fc receptor-mediated splenic clearance function in 32 patients. Clearance half-times were prolonged in patients with lupus erythematosus compared with those in normal controls (p < 0.0001) and longer in patients with renal disease than in those without (p < 0.025). Both renal (tau = 0.45, p < 0.0002) and nonrenal (tau = 0.35, p < 0.003) disease activity were significantly but independently associated with clearance half-times. When matched for nonrenal activity, patients with nephritis had greater clearance dysfunction than their counterparts without renal disease. Circulating immune complexes did not correlate with clearance for all patients. Neither B8 not DR3 histocompatibility antigen markers differentiated the renal and nonrenal disease subgroups. The greater Fc receptor-mediated clearance dysfunction, which occurs in patients with lupus erythematosus and nephritis, could lead to enhanced glomerular deposition of immune complexes as a primary event, or as a secondary event amplifying previously established lesions.