ABSTRACT: The thromboresistance of endothelium is maintained as long as natural anticoagulant pathways are functionally present on endothelial plasma membranes. The principal anticoagulant pathways in human hearts and kidneys are thrombomodulin (TM) and heparan sulfate proteoglycan-antithrombin III (HSPG-ATIII). The downregulation of TM or the loss of ATIII is associated with fibrin deposition. This sequence of events occurs when stable allografts of hearts or kidneys become unstable or rejected. Human placentae do not contain the HSPG-ATIII natural anticoagulant pathway, but the TM system is uniformly represented on endothelium of normal chorionic villi. However, many villi in placentae from preeclamptic pregnancies contain thrombomodulin-negative endothelium, and these vessels contain fibrin thrombi. These thrombi compromise blood flow through the placental microcirculation and are associated with ischemic changes either with or without the presence of cellular infiltrates.