We characterized the cause of two cases of transitory acquired von Willebrand syndrome associated with the administration of ciprofloxacin. Purified Ig from the two patients did not inhibit Ristocetin Cofactor activity or binding to collagen of normal plasma, ruling out the possibility of an inhibitor. The analysis of multimeric pattern of plasma von Willebrand Factor (vWF) showed the lack of larger multimers in both patients, with a relative decrease of all the remaining forms in the first patient. The subunit composition of plasma vWF showed a marked reduction of the native 225 Kd subunit (31.9% and 32.9%; normal range 74-86%) and an increased proportion of the 189, 176, and 140 Kd fragments. These abnormalities disappeared during the follow-up, without any specific therapy. In conclusion, a common pathophysiological basis is demonstrated in both patients, with a heightened proteolysis of plasma vWF by an unknown mechanism.