The differentiation of type IIb von Willebrand's disease from other variants of von Willebrand's disease, especially platelet-type (pseudo-) von Willebrand's disease, poses a significant clinical problem because, although they are similar in the clinical and diagnostic laboratory settings, the therapy of type IIb von Willebrand's disease is different from the therapy of platelet-type von Willebrand's disease. This discrimination has required cumbersome assays using fresh platelet-rich plasma that often yielded equivocal results. Because it was shown by other researchers that type IIb von Willebrand factor binds to normal platelets with increased avidity at low concentrations of ristocetin, it was reasoned that von Willebrand factor from patients with type IIb von Willebrand's disease would also bind to formalin-fixed washed platelets at low concentrations of ristocetin. Using the radiolabeled "neutral" monoclonal antibody AVW1 to label plasma von Willebrand factor, the binding of von Willebrand factor to formalin-fixed washed platelets was studied as a function of ristocetin concentration. These studies demonstrated that the 125I-AVW1 von Willebrand factor from 13 patients with type IIb von Willebrand's disease binds to formalin-fixed washed platelets at significantly lower concentrations of ristocetin than plasma von Willebrand factor from 18 normal individuals, 3 patients with platelet-type von Willebrand's disease and 8 patients with other variant forms of von Willebrand's disease. This radiolabeled "neutral" monoclonal antibody technique provides a rapid, simple method for the differentiation on frozen plasma samples of type IIb von Willebrand's disease from platelet-type and other variants of von Willebrand's disease.