Glycoprotein (GP) Ib (α and β) in platelets forms a noncovalent hetero-oligomeric complex with GPIX and GPV and serves as a receptor for von Willebrand factor (vWF), which mediates the initial adhesion of platelets to the subendothelium after vascular damage and also plays a role in thrombin-induced platelet activation. We investigated the interaction between GPIbα and FcγIIA receptor using a yeast two-hybrid system and mutagenesis, and we identified residues R542G543R544 in GPIbα and D298D299D300 in FcγIIA receptor as the primary interaction sites. These results further confirmed the interaction between GPIbα and FcγIIA receptor and support the hypothesis that the signal transduction of GPIb-IX-V that leads to platelet activation may be partially mediated through FcγIIA receptor.