HL-60 cells derived from a human promyelocytic leukemia underwent apoptosis by heat treatment. When the heat-treated HL-60 cells were injected into guinea pig skin, monocyte/macrophage infiltration was observed 24 or 36 hours later, and the apoptotic cells were phagocytically cleared by 48 hours after their injection. The infiltration and clearance patterns were quite different from those observed in injection of necrotic or boil-fixed HL-60 cells. The apoptotic cells released a monocyte chemotactic factor in vitro 24 hours after the heat treatment. The chemotactic factor generated was identified as the cross-linked homodimer of S19 ribosomal protein by its immunologic and physicochemical properties. A serine protease that inactivates the monocyte chemotactic factor was also released from the apoptotic cells 30 hours after the heat treatment. A super infusion of this protease into the skin where the apoptotic cells had been injected diminished the number of infiltrated monocytes. The present results indicate an important role of the S19 ribosomal protein dimer in the phagocytic clearance of apoptotic cells.