The expression of tissue factor (TF), the initiator of the clotting system, was investigated by immunohistochemical staining for its role in clotting mechanisms of Plasmodium falciparum-infected placenta. Most mononuclear cells in the intervillous space of infected placentas stained with an anti-TF monoclonal antibody (MAb) and were positive for antimacrophage MAb. The intervillous space of infected placentas had significant fibrin deposition. In contrast, only small amounts of leukocytes, TF-positive cells, and fibrin were seen in the intervillous space in noninfected placentas. These results indicate that macrophages accumulated in infected placentas express TF and that subsequent perivillous fibrin clot formation leads to a narrowing and plugging of the intervillous space and disturbance of the blood supply. Macrophage TF expression in placentas could be associated with retarded placental growth and low birth weight in malaria infection and should be further investigated.