Human von Willebrand factor (vWF) is synthesized as an extra large polymer; then, it is converted to lower molecular weight plasma multimers, originally composed of intact 225-kDa subunits, by a metalloproteinase. Proteolysis generates two fragments of 140-and 176-kDa, which originate from cleavage of peptide bond Tyr842-Met843 and which represent vWF residues 1-842 and 843-2050, respectively; a very small amount of 189-kDa fragment can also be found in normal plasma. We describe here a two-dimensional (2-D) method to analyze plasma vWF structure.