The overall goal of this Program Project is to understand how the processes of coagulation, thrombosis and fibrinolysis are initiated, regulated and terminated. This goal includes obtaining a fundamental understanding of the interrelationships between these processes, and ultimately obtaining the means to rationally manipulate them for diagnostic and therapeutic purposes. One of the concepts that has become increasingly clear is that much of the regulation of coagulation and fibrinolysis takes place through the assembly of macromolecular complexes on membrane and fibrin surfaces. Therefore, while we will study the functional properties of individual molecules, our emphasis is on those characteristics which pertain to the regulation of that molecule's function. This approach includes studies of macromolecular assemblies utilizing model systems such as synthetic vesicles, as well as platelets, fibrin and endothelial cells. There are also studies aimed at determining those characteristics of the vitamin K- dependent coagulation factors which result in regulation of expression at the level of carboxylation and thus the membrane binding phenomenon. The composite of the four projects and the two cores of this program will lead to detailed investigations of surface dependent reactions specific in thrombosis and thrombolysis, however, the principles discovered have ubiquitous applications in biology.