It was examined whether or not steroid and reticuloendothelial system (RES) stimulants had any effect on serum clearance and tissue uptake of aggregated human IgG (AHG), as a model of soluble immune complexes, in mice. Eighty percent of the AHG administered cleared from circulation within 1 hr, predominantly by the liver and partially by the spleen in control mice. The clearance of AHG was delayed (p<0.001) in steroid-treated mice. This was most prominent when mice were treated with 200mg/50kg PSL for one week. After administration of 1000mg/50kg Methyl-PSL for 3 days serum AHG clearance was less than after adminstering 50mg/50kg PSL. Suppression of RES by steroid increased the accumulation of AHG in the kidney (p<0.05), possibly by inhibiting hepatic uptake of AHG. PVP and LPS unexpectedly suppressed RES function. Zymosan had no effect on RES function. It was found that suppresion of RES was the main factor in induction of tissue damage (nephropathy) due to delay in the clearance of soluble immune complexes and increased the deposition of that into the kidney.