Lewis rats were given a single intravenous injection of soluble immune complexes, composed of human serum albumin and rabbit anti-human serum albumin, prepared with either whole antiserum or purified IgG antibodies. The animals were sacrificed at intervals ranging from 2 to 24 hours, and Fc and C3 receptor activities of Kupffer cells were studied in Kupffer cell-enriched suspensions and in frozen sections of liver, using red cell rosetting techniques employing IgGEA and IgMEAC reagents. At 2 to 12 hours, there was reduction or loss of Fc and C3 receptor activity. The extent of reduction correlated with the amount of complexes injected. Both C3 and Fc receptor activity returned to normal levels within 24 hours. Immunofluorescence revealed rabbit IgG in numerous Kupffer cells at 2 hours, but in almost none at 6 to 12 hours after injection. 125I trace-labeled immune complexes were shown to be cleared more slowly than normal in animals injected 2 hours earlier with immune complexes. The findings show that circulating immune complexes can produce loss of Fc and C3 receptor function of Kupffer cells in vivo and provide evidence that this can result in diminished clearance of complexes.