Fibrin(ogen) deficiency (Fg^-/-) was shown previously to be compatible with rapid thrombus growth within injured arterioles, but platelet fibronectin content was increased and newly formed thrombi were unstable. To further define the role of fibrin(ogen) in thrombus formation and stabilization, platelet biology was examined in mice expressing a form of fibrinogen that clots normally but lacks the γ chain C-terminal binding site for αIIbβ3 (FgγΔ5). Thrombus growth within the arterioles of FgγΔ5 mice appeared faster than in wild-type mice despite a far greater emboli formation. Unlike Fg^-/- mice, the emboli were relatively small and released from the top of thrombi, rather than by fracture at the vessel wall. The fibronectin content in FgγΔ5 platelets was also dramatically increased through a β3 integrin-dependent mechanism. The following has been concluded: (1) Fibrin formation contributes to, but is not sufficient for, the stabilization of arterial thrombi. Platelet receptor engagement of the C-terminal of the Fg γ chain contributes to the stable incorporation of platelets into thrombi. (2) Alternative ligands to fibrinogen can support efficient thrombus growth. (3) Fibrinogen is internalized through αIIbβ3 engagement of the fibrinogen γ chain element, and this interaction secondarily controls the fibronectin content of platelets. (Blood. 2003;102: 3609-3614)