The goal of these experiments is to characterize the reactions which constitute the contact phase of intrinsic clotting. They are designed to establish the intermediate reactions which take place between contact activators and purified factors XI, XII, high molecular weight kininogen (contact activation cofactor, Fitzgerald factor) and prekallikrein (Fletcher factor), which lead to the formation of activated factor XI. The reaction of contact activators with different combinations of purified reactants in isolated systems will be evaluated, and active intermediates will be isolated and characterized by immunologic and biochemical techniques. The relationship of the structure of high molecular weight kininogen to its participation in these reactions will be investigated.