The protein C anticoagulant pathway represents a newly described system for investigating the regulation of blood coagulation. A role for protein C in clinial thrombosis has been suggested by recent findings that patients with 50% normal levels of protein C are at rick of thrombosis and that protein C levels decrease markedly during intravascular coagulation. The data presented here suggest that deficiencics in protein S, thrombomodulin, or the platelet receptor for activated protein C might also result in a thrombotic tendency. The interplay among the cellular, vascular and humoral components in this system suggest that the protein C anticoagulant pathway may be perturbed by a variety of disease processes. Certainly, the system provides a new approach to investigate the molecular basis of thrombotic disease.