The susceptibility of von Willebrand factor (VWF) of blood group O, A, B and AB to proteolysis by the ADAMTS13 metalloprotease was investigated. Multimeric analysis indicated that the rate of VWF proteolysis differed between blood groups and was greater for group O VWF than for non-O VWF in the rank order O >/= B > A >/= AB. Measurement of the collagen binding activity of VWF of each blood group following proteolysis for a fixed time interval corroborated the results obtained on multimer analysis: the loss of collagen binding activity was greater for VWF of group O compared with non-O VWF, in the rank order O >/= B > A >/= AB. Ristocetin was found to increase the rate of VWF proteolysis approximately two-fold; the differential between blood groups was retained in the presence of ristocetin.