In this communication some of the important regulatory mechanisms involving endothelial cell surface associated anticoagulant reactions as well as endothelial cell surface expressed receptors which directly contribute to the inhibition of coagulation are reviewed. In particular, the mechanism of action of protease inhibitors such as antithrombin III, heparin cofactor II, or protease nexin I and their possible interaction with glycosaminoglycan components of the endothelial cells is critically summarized. Thrombin binding to endothelial cells, in particular to thrombomodulin, is believed to be a major event in the induction of anticoagulatory mechanisms such as the protein C/protein S system which warrant a balanced hemostatic system. Additional components such as vascular anticoagulant or extrinsic pathway inhibitor may also contribute to the anticoagulant potential of the vessel wall. Furthermore, the modulation of these membrane-associated anticoagulant reactions by other components such as heparin-binding proteins is discussed.