Platelet membrane glycoprotein (GP) Ibα, a component of the GP Ib-IX-V complex, is a receptor for von Willebrand factor (VWF). A small quantity of large VWF multimers binds to platelets under high shear stress, and induces aggregation. We studied the shear-induced attachment of large and unusually large VWF multimers to the GPIbα extracellular domain (glycocalicin), human platelets, and GPIbα gxpressing Chinese hamster ovary (CHO) cells. Compared to binding in the presence of botrocetin and ristocetin, shear stress only induced low-level NVWF (normal plasma VWF multimers) binding. This shear stress induced interaction is also dependent on VWF multimeric size. Elevated binding levels of endothelial cell VWF (enriched in unusually large VWF multimers) to glycocalicin-coated beads were observed under low shear conditions, which did not result in the attachment of normal plasma VWF.