Immune complexes (IC), after reacting with the complement system, bear C3b fragments (opsonized IC) and bind to the CR1 receptor that is present on human erythrocytes (CR1 = complement receptor type 1). This efficient binding reaction prevents random vascular IC deposition, and allows IC to be transported through the circulation to the fixed macrophage system of the liver and spleen, where they are safely eliminated. The structure of CR1, with multiple C3b binding sites, and the clustered distribution of CR1 on the erythrocyte surface favor the multivalent binding of opsonized IC to erythrocytes. CR1 on erythrocytes serves as a cofactor for the inactivation of C3b by factor I, thus allowing the release of IC from the erythrocyte surface and their transfer to fixed macrophages. Under normal circumstances, the erythrocyte plays a major role in the processing of IC in humans.