The interaction of platelets with collagen is a complex reaction because collagen monomer does not have any affinity to platelets, but collagen fibrils and immobilized collagen bind strongly to platelets. It was postulated that a platelet would have multiple binding sites for collagen that would encompass several collagen molecules polymerized to each other. The mechanism for how these collagen fibrils or immobilized collagen bind to and activate platelets is still unknown. Two platelet glycoproteins, GP Ia/IIa (integrin alpha 2 beta 1) and GP VI, fulfill the following requirements for a physiological collagen receptor: 1) antibodies against these proteins inhibit the platelet aggregation induced by collagen and platelet adhesion to collagen under both static and flow conditions, and 2) patients whose platelets are deficient in either GP Ia/IIa or GP VI have been found, and their platelets show no interaction with collagen. Under flow conditions, which closely approximate physiological conditions under which thrombus formation occurs, platelets interact with vWf molecules bound to immobilized collagen and then the adhered platelets would react with collagen through their collagen receptors, resulting in activation of the platelets and subsequent formation of platelet aggregates. Although the details of the interaction of GP Ia/IIa with collagen have been investigated in recent years, the mechanism of the reaction between GP VI and collagen remains to be explored.