Integrin ␣IIb3 is the major membrane protein and adhesion receptor at the surface of blood platelets, which after activation plays a key role in platelet plug formation in hemostasis and thrombosis. Small angle neutron scattering (SANS) and shape reconstruction algorithms allowed formation of a low resolution three-dimensional model of whole ␣IIb3 in Ca 2؉ /detergent solutions. Model projections after 90°rotation along its long axis show an elongated and "arched" form (135°) not observed before and a "handgun" form. This 20-nm-long structure is well defined, despite ␣IIb3 multidomain nature and expected segmental flexibility, with the largest region at the top, followed by two narrower and smaller regions at the bottom. Docking of this SANS envelope into the high resolution structure of ␣IIb3, reconstructed from crystallographic and NMR data, shows that the solution structure is less constrained, allows tentative assignment of the disposition of the ␣IIb and 3 subunits and their domains within the model, and points out the structural analogies and differences of the SANS model with the crystallographic models of the recombinant ectodomains of ␣IIb3 and ␣V3 and with the cryo-electron microscopy model of whole ␣IIb3. The ectodomain is in the bent configuration at the top of the model, where ␣IIb and 3 occupy the concave and convex sides, respectively, at the arched projection, with their bent knees at its apex. It follows the narrower transmembrane region and the cytoplasmic domains at the bottom end. ␣IIb3 aggregated in Mn 2؉ /detergent solutions, which impeded to get its SANS model.Blood platelets have distinct mechanisms to respond to the different agonists of platelet activation, all of which end up with the acquisition by the integrin ␣IIb3 or glycoprotein IIb/IIIa of the capacity to recognize and bind fibrinogen and other adhesive proteins. Binding of fibrinogen, the major adhesive protein in plasma, to activated ␣IIb3 and the binding of fibronectin, the major adhesive protein in the extracellular matrix of subendothelium, to resting or activated ␣IIb3 lead to the formation of interplatelet cross-linking and to platelet adhesion to the subendothelium, respectively, and, eventually, to the formation of the platelet plug. Thus, knowledge of the fibrinogen receptor and the mechanisms of induction and modulation of its activity is determinant to understand hemostasis and the pathophysiological paths leading to thrombosis, as well as to develop new ways to prevent, detect, and treat thrombosis effectively, securely, and selectively. After 20 years of molecular genetics and 10 years of high resolution structural biology of integrins, the disposition of an integrin in the membrane is unknown, the modifications in the cytoplasmic domains and the transmembrane segments related with the receptor activation are still not definitively defined, and the molecular mechanism of activation and molecular properties of the activated receptor are still under discussion (1-4). Structural and cell biological informat...