The interaction of von Willebrand factor (vWF) with the platelet receptor glycoprotein Ib␣ (GPIb␣) is important for platelet adhesion at high shear stress. Two functionally important antigenic areas within GPIb␣ were identified through the characterization of 5 new inhibitory anti-GPIb monoclonal antibodies (mAbs). The binding sites of 3 of these anti-GPIb mAbs, which were intercompeting and potently inhibiting shear stress-induced binding of vWF, were mapped within the N-terminal amino acid (aa) 1-59 area by the use of canine-human chimeras. These antibodies, however, had little or no effect (approximately 40%