The endothelium plays an active role in the regulation of the coagulation mechanism. Multiple anticoagulant properties are operative on the cell surface in homeostasis. In the protein C/protein S pathway, for example, endothelium provides cofactors promoting activation of protein C, assembly of the activated protein C/protein S complex, and synthesizes protein S. In contrast, following exposure to cytokines and other pathologic stimuli, endothelial cell activation occurs. This activated state includes upregulation of procoagulant properties, such as tissue factor, with concomitant downregulation of anticoagulant cofactors, such as thrombomodulin. Modulation of endothelial cell coagulant properties by cytokines provides a mechanism linking activation of the clotting mechanism to the cellular response to environmental stimuli.