The clearance of erythrocytes sensitized with IgG was studied in MRL/Mp-lpr/lpr (MRL-lpr) and MRL/Mp-+/+ (MRL-+/+) mice, which spontaneously develop autoimmune disease. In both strains, an age-dependent decline in clearance of IgG-sensitized erythrocytes was found. Impaired clearance occurred at an earlier age in MRL-lpr mice than in MRL-+/+ mice, correlating with the relative severity of autoimmune disease in these strains. Androgen treatment improved clearance in MRL-+/+ mice but not in MRL-lpr mice, even though autoantibody levels, renal function, and survival were improved. These results suggest that the beneficial effects of androgen on autoimmune disease are not due solely to improved clearance of immune complexes. Castration followed by estrogen administration did not influence immune clearance or autoimmune disease in MRL-lpr mice. These results indicate that impaired immune clearance is a common feature in several autoimmune mouse strains. However, the effects of sex hormones on immune clearance and autoimmune disease may be dissociated in some strains.