The present research program is focused on 1) determining the primary structure of human factor XII and the functional role of specific regions in the molecule, 2) the isolation and characterization of human factor VIII and defining on a molecular basis its mechanism of action in blood coagulation, 3) examining the binding and activation of coagulation factors on endothelial cells, 4) a study of the role and biosynthesis of Beta-hydroxyaspartic acid, 5) investigating the possible role of kallikrein, factor XIIa, factor XIa, and other serine proteases in the activation of tissue plasminogen activator, and 6) the characterization of the cDNAs and genes for prothrombin, factors VII, X, XI, XII, Von Willebrand factor, protein C, and plasminogen. These studies will employ different techniques for protein isolation and characterization and will complement investigations employing methods of recombinant DNA. A more detailed understanding of the structure, function, mechanism of action and the biosynthesis and regulation of the proteins involved in blood coagulation and fibrinolysis hopefully will provide new and important information on how blood clots are formed and how they are dissolved under various physiological conditions. This type of information is essential for an intelligent clinical management of individuals who suffer from vascular damage or injury or various coagulation disorders such as hemophilia. Furthermore, abnormal coagulation and fibrinolysis are associated directly or indirectly with vascular diseases such as coronary thrombosis, cerebral thrombosis and deep vein thrombosis. Basis research that will add to our fundamental understanding of these processes and assist the physician in the prevention of an abnormal thrombus is essential in the proper treatment of these diseases that lead to the death of more than 50% of the American population.