Apoptotic cells activate homologous complement and are opsonized with iC3b. We assessed the effect of iC3b opsonization upon phagocytosis of apoptotic Jurkat cells by macrophages, which were differentiated from THP-1 cells by treatment with retinoic acid. Macrophage phagocytosis of apoptotic Jurkat cells was enhanced upon incubation of the apoptotic cells with normal human serum. The enhanced macrophage phagocytosis of normal serum-treated apoptotic cells was decreased by anti-human C3 F(ab')2 and anti-CR3 and anti-CR4 mAbs to the level of phagocytosis of those treated with complement-blocked serum. These results suggest that interaction between iC3b on apoptotic cells and complement receptor type 3 (CR3) and/or complement receptor type 4 (CR4) on macrophages could play an important role for the clearance of apoptotic cells by macrophages in vivo.