The proposed work has two principal objectives: 1) development of hydrophobic adsorption chromatography as a method of improving factor VIIII von Willebrand protein (VIIIR:WF protein) purification; 2) elucidation of factor VIII structure and function with the aid of 125I-labeled antibodies directed against VIIIR:WF protein and factor VIII coagulant antigen (VIII:C (Ag). Our preliminary experiments with the hydrophobic adsorbant phenyl-sepharose have shown this material to have a high affinity for fibrinogen and a much lower one for factor VIII. Variables such as ionic strength, temperature and hydrophobic eleuting buffer have been manipulated to achieve maximum yield and purification. The improved purification procedure will be helpful in acquiring factor VIII for further research purposes. The structure of VIII:WF protein and VIII:C (Ag) will be examined by use of 1 and 2 dimension SDS gel electrophoresis, agarose gel electrophoresis and isoelectric focusing. Techniques employing 125I-labeled antibodies to these proteins will be used to discern differences in protein structure between normal individuals and those with VIII abnormalities.