Studies were initiated to isolate and characterize an antibody to von Willebrand Factor that developed in an individual with a benign monoclonal gammopathy. The plasma of this individual has been previously shown to contain an antibody that binds to vWF without affecting the ability of von Willebrand factor to aggregate platelets. The monoclonal spike has been determined to be IgG, by radial immunodiffusion. IgG has been isolated from the patient's plasma by 2 different methods, affinity chromatography on Protein A Agarose and ion exchange chromatography on QAE. We have attempted to isolate antibody specific for vWF by affinity chromatography with immobilized vWF. To date we have been unable to recover any detectable antibody. Radiolabeled patient IgG has been incubated with von Willebrand Factor and the immune complexes isolated by gel filtration chromatography. Radioactivity in the immune complex fraction was barely detectable suggesting that the specific antibody represents a very small percentage of the purified patient IgG.