This study examined the mononuclear phagocyte system (MPS) capacity to eliminate IgG-sensitized syngeneic erythrocytes (EA) after antigenic challenge. Survival data of EA in normal and preimmunized mice showed that a single dose of T-dependent antigen was able to delay Fc gamma R-dependent clearance. This impairment in EA elimination was dependent on the dose of antigen injected. On the other hand, T-independent antigens, B cell mitogen, and the inflammatory agent Freund's incomplete adjuvant were ineffective in modulating MPS function. As expected, the liver and the spleen were the main sites of EA trapping, but the spleen of immunized mice sequestered significantly less EA than that of control mice. Impaired clearance capacity was observed as soon as 24 hr after immunization and was persistent up to the seventh day after antigenic stimulation. Moreover, mice decomplementation by cobra venom factor treatment did not prevent the impairment of MPS by antigenic stimulation, suggesting that it is strictly Fc gamma R dependent. Our results indicate that stimulation of the immune system by T-dependent antigens can diminish the Fc gamma R-mediated clearance capacity of the MPS. The possible mechanisms involved in this regulation are discussed.