Classification of the subtypes of von Willebrand's disease (vWd) has been based on a quantitative deficiency or an abnormal multimeric composition of von Willebrand factor (vWf). Although the co-deficiency of a second protein, von Willebrand's antigen II (vW AgII), had been previously recognized, its concentration in a relatively large number of normal individuals or patients with well-defined vWd variants had not been studied. The plasma from patients with type I, IIA, IIB, IIC, and III (severe) vWd was evaluated, and the concentrations of vW AgII and vWf were determined. Although patients with type I and III vWd had reduced levels of both proteins, the plasma vW AgII concentration was normal in patients with type II vWd. Analysis of the results indicates that type I and type II variants can be discriminated with greater than 80% accuracy by comparison of results of these two antigenic assays. The normal levels of vW AgII in type II variants suggest a possible difference in the pathophysiology of type I and type II vWd.