It has long been known that the ITIM-bearing IgG Fc receptor (FcγRIIb, RIIb) is expressed on liver sinusoidal endothelial cells (LSEC) and that the liver is the major site of small immune complex (SIC) clearance. Thus, we proposed that RIIb of LSEC eliminates blood-borne small immune complexes (SIC), thereby controlling IC-mediated autoimmune disease. Testing this hypothesis we found most RIIb of the mouse, fully three-quarters, to be expressed in liver. Moreover, most (90%) liver RIIb was expressed in LSEC, the remainder in Kupffer cells (KC). An absent FcRγ in LSEC implied that RIIb is the sole FcγR expressed. Testing the capacity of liver RIIb to clear blood-borne SIC we infused mice intravenously with radioiodinated SIC made of ovalbumin and rabbit IgG anti-ovalbumin. Tracking decay of SIC from the blood, we found the RII KO strain to be severely deficient in eliminating SIC compared with the WT strain, terminal half-lives being, respectively, 6 and 1.5 hours. RIIb on LSEC, a major scavenger, keeps SIC blood concentrations low and minimizes pathologic deposition of inflammatory IC.