A 22 year-old woman with diabetes insipidus on chronic therapy with desmopressin acetate (DDAVP) developed recurrent venous thromboembolism and transient thrombocytopenia temporally related to the administration of DDAVP. Large increases in plasma von Willebrand factor (vWF), vWF-activity, and relative increases in the concentrations of the larger multimeric forms of vWF-antigen were observed, as well as a plasma factor which sensitized normal platelets to undergo spontaneous aggregation in vitro. Additional studies showed that the patient's plasma retained the platelet aggregation inducing activity after selective removal of vWF by immunoabsorption. The nature of the platelet activating factor and the relationship of this factor and the excessively increased and transiently abnormal vWF to the recurrent venous thromboembolism in this patient remain uncertain. Although the findings do not implicate definitively DDAVP in the elevation of vWF in this patient, it is suggested that its use be considered with caution in patients with diabetes mellitus and increased levels of vWF.