Complement participates in the elimination of IC in many circumstances. When antigen/antibody IC first form in the circulation, complement inhibits their aggregation because the covalent binding of C3b to the IC modifies their biophysical properties and they remain soluble. Such opsonized (C3b coated) IC attach to cells bearing C3b receptors (CR1) in the circulation, in particular to erythrocytes, since in humans 85 to 90% of CR1 in the blood is located on these cells. This immune adherence binding reaction appears to be a physiological system that allows IC to be transported through the circulation to the fixed macrophages of the MPS where they are safely eliminated. The deposition of circulating complement-fixing IC in various organs such as the kidney may be considered as a failure of this transport system. This is apparent in complement deficient and depleted states, and also for non-complement-fixing IC (IgA IC). The formation of insoluble IC (by definition immune deposits found in human pathology are insoluble) produces complement activation and inflammation at the site of the immune aggregate.