Integrins are a large family of heterodimeric transmembrane signaling proteins that affect diverse biological processes such as development, angiogenesis, wound healing, neoplastic transformation, and thrombosis. We report here the three-dimensional structure at 20-Å resolution of the unliganded, low-affinity state of the human platelet integrin α_IIbβ₃ derived by electron cryomicroscopy and single particle image reconstruction. The large ectodomain and small cytoplasmic domains are connected by a rod of density that we interpret as two parallel transmembrane α-helices. The docking of the x-ray structure of the α_Vβ₃ ectodomain into the electron cryomicroscopy map of α_IIbβ₃ requires hinge movements at linker regions between domains in the crystal structure. Comparison of the putative high- and low-affinity conformations reveals dramatic conformational changes associated with integrin activation.