The splenic component of the mononuclear phagocyte system (MPS) was investigated in the rat using N-ethylmaleimide-treated erythrocytes (NEM) and erythrocytes coated with a monoclonal IgG2b antibody (R3/13) directed against the rat RT1Aa major histocompatibility antigen. Both cell suspensions were removed by the spleen, and their clearance times were significantly longer in splenectomized animals. The mean clearance times for the NEM-treated cells in both normal and cobra venom-treated rats were similar (19.1 +/- 1.1 min and 19.0 +/- 1.0 min, respectively) but differences were seen between the clearance of R3/13 antibody-sensitized cells in these two groups (normal rats 38.3 +/- 2.8 min and CVF-treated rats 51.7 +/- 4.2 min, P less than 0.02). Different receptors were also involved in the removal of these cells; in normal animals recognition entailed interaction with complement receptors, whereas in CVF-treated animals this was implemented by Fc receptors. Complement activation prolonged the clearance rates of both R3/13 cells and NEM cells in normal animals, but the effect of complement activation on the clearance of NEM-treated cells was achieved via changes in splenic blood flow. When this was prevented from taking place no effect was seen on the clearance of NEM cells, although the clearance of R3/13 cells was inhibited by the complement fragments generated by complement activation.