The goals of these experiments are to purify and characterize a previously unrecognized plasma activity ("contact activation cofactor") which participates with factors XI and XII in the contact activation of intrinsic clotting, and to study the mechanism by which this activity interacts with the other known reactants in this system. Contact activation cofactor will be purified from normal human plasma using standard biochemical techniques such as ammonium sulfate fractionation, specific adsorbants, ion exchange and adsorption chromatography, gel filtration, electrophoresis. Factor XI, factor XII, and Fletcher factor will be prepared from normal human plasms by modification of published techniques. The interactions of these individual activities will be studied to clarify the intermediary reactions which together make up the process of contact activation.