Acquired von Willebrand disease (vWD) has been described in a few patients with multiple myeloma. The present study characterizes an inhibitor of von Willebrand factor (vWF) isolated from a patient with multiple myeloma (IgG-kappa). Multimeric analysis of vWF from this patient's plasma showed a reduction in multimers of all sizes. The inhibitor (IgG) detected only the vWF subunit from plasma of normal individuals. It reacted with intact vWF subunit and a 39/34kDa dispase-digested fragment of vWF (residues; Leu480/Val481-Gly718), but did not react with platelet membrane glycoproteins (GPs) or adhesive proteins. The binding of vWF to GPIb mediated by ristocetin and by botrocetin was inhibited by the patient's IgG with an IC50s of 0.3 mg/ml and 0.48 mg/ml, respectively. The platelet aggregation induced by ristocetin or botrocetin was also inhibited by the IgG. These results indicate that this inhibitor may recognize the binding region of vWF to GPIb. Therefore, the antibody to vWF appears to represent the likely pathophysiological mechanism responsible for the acquired vWD in this patient.