The hepatic and splenic uptake of circulating, small-latticed immune complexes and the effect of these complexes on the hepatic mononuclear phagocyte system (MPS) were examined in mice. The small-latticed immune complexes were prepared at fifty-fold antigen excess. The clearance from circulation and uptake by the liver and spleen of two probes of MPS function, aggregated human IgG and aggregated mouse albumin, were quantified. The hepatic uptake of a dose of small-latticed complexes, containing 5 mg of antibodies, at 1 hr was comparable with the uptake of a similar dose of complexes that contained large-latticed complexes. At later time points, the hepatic uptake of the small complexes was significantly less than that of the larger complexes. The splenic uptake of the small-latticed complexes was less at all time points. Doses of the small-latticed complexes, ranging from 1 to 5 mg antibody in the complexes, produced no significant inhibition of the clearance or organ uptake of the MPS probes when administered 1 hr after the preload injections. In contrast, large-latticed complexes produced a dose-dependent delay in clearance due to a decreased hepatic uptake of the probes. These observations showed that small-latticed immune complexes were ineffectively removed by the hepatic MPS and that the presence of large quantities of small-latticed complexes in circulation did not alter MPS function.