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This review summarises some of the key developments that have taken place in our understanding of platelet-collagen interactions within the last 18 months. Within this time, the major activatory collagen receptor glycoprotein VI (GPVI) has been sequenced and shown to reconstitute collagen responses in a megakaryocytic cell line. It is a member of the Ig superfamily of proteins, with two extracellular Ig domains, and is constitutively associated with the Fc receptor γ-chain (FcR γ-chain). GPVI signals through a pathway that shares many features with those of immune receptors, with critical roles for Syk and the adapters LAT and SLP-76 in the activation of PLCγ2. Significant developments have also taken place in regard to the role of the major adhesion receptor for collagen, the integrin α2β1 (also known as GPIa-IIa). An α2β1-selective collagen-based peptide has been developed and co-crystalisalised with the I-domain of the α2 subunit. Polymorphisms in α2 have been shown to cause wide variation in expression of α2β1, with the α2 allele T[sub 807]/A[sub 873] leading to a high level of the integrin and increased risk of stroke in young people. Activation of platelets by a wide range of agonists has been shown to increase the affinity of α2β1 to intermediate or high affinity states. This has important implications for the two-site, two-state model of collagen-platelet interactions. A new model is proposed in which collagen binds initially to either α2β1 or GPVI, leading to subsequent binding to the other receptor and conversion of the integrin to a high affinity state. In this model, both receptors generate intracellular signals which support platelet activation. [ABSTRACT FROM AUTHOR]