When platelets are stimulated by agonists, integrin alpha (2)beta (1) (GP Ia/IIa), one of the platelet collagen receptors, is activated to forms with high affinities for its ligan collagen. Here we describe our studies to characterize the binding kinetics of the activated integrin forms and the activation mechanism. Under low agonist concentrations, integrin alpha (2)beta (1) is activated through a mechanism involving ADP/ADP receptors; and under high agonist concentrations, multiple signaling pathways and involved in its activation. Such differences in mechanism at low an high agonist concentrations are also suggested in the activation of integrin alpha (I1b)beta (3), the platelet fibrinogen receptor. We describe our flow adhesion studies, from which evidence was obtained about the involvement of integrin alpha (2)beta (1) activation in the physiological function of platelets, adhesion and thrombus formation. (Trends Cardiovasc Med 2000;10:285-292). (C) 2001, Elsevier Science Inc.