The inhibitor-neutralizing capacity of the plasmas of 101 patients with hemophilia A and 16 with was deter- Factor mined, using a natural antibody against factor VIII. In 48 patients with severe hemophilia A, no inhibitor- neutralizing material was detectable. The plasmas of Von Willebrand’s disease 47 patients with moderate or mild hemophilia A contained inhibitor-neutralizing material in amounts equivalent to the biological activity. In 6 patients with hemophilia A (factor activity ranging from 3.2-26%), from 5 kindreds more inhibitor-neutralizing material was found as expected from the biological activity, indicating the presence of inactive, probably structurally abnormal factor VIII. Inactive factor VIII was not found in plasmas of patients with von Willebrand’s disease.