Collagen stimulates platelet activation through a tyrosine kinase–based pathway downstream of the glycoprotein VI (GPVI)–Fc receptor (FcR) γ-chain complex. Genetic ablation of FcR γ-chain results in a complete inhibition of aggregation to collagen. In contrast, a steady increase in light transmission is induced by collagen in phospholipase Cγ2–deficient (PLCγ2^–/–) platelets in a Born aggregometer, indicating a weak level of activation. This increase is inhibited partially in the presence of an α₂β₁-blocking antibody or an α_IIbβ₃ antagonist and completely by a combination of the 2 inhibitors. It is also abolished by the Src kinase inhibitor PP1 and reduced in the presence of the phosphatidylinositol (PI) 3-kinase inhibitor wortmannin. The GPVI-specific agonists convulxin and collagen-related peptide (CRP) also stimulate weak aggregation in PLCγ2^–/– platelets, which is inhibited by wortmannin and PP1. Collagen and CRP stimulate tyrosine phosphorylation of PLCγ1 at its regulatory site, Tyr 783, in murine but not in human platelets through a Src kinase–dependent pathway. Adhesion of PLCγ2^–/– platelets to a collagen monolayer is severely reduced at a shear rate of 800 s^–, relative to controls, whereas it is abolished in FcR γ-chain^–/– platelets. These results provide strong evidence that engagement of GPVI stimulates limited integrin activation in PLCγ2^–/– platelets via PLCγ1 and PI3-kinase.