Adenosine diphosphate (ADP) is an important platelet agonist and ADP released from platelet dense granules amplifies responses to other agonists. There are three known subtypes of ADP receptor on platelets: P2X₁, P2Y₁ and P_2T receptors. Sustained ADP‐induced aggregation requires co‐activation of P2Y₁ and P_2T receptors. AR‐C69931MX, a selective P_2T receptor antagonist and novel antithrombotic agent, was studied to characterize further the function of the P_2T receptor. The roles of the P2Y₁ receptor and thromboxane A₂ were assessed using the selective P2Y₁ antagonist A2P5P and aspirin respectively. Aggregation was measured by whole blood single‐platelet counting and platelet‐rich plasma turbidimetry, using hirudin anticoagulation. Dense granule release was estimated using [¹⁴C]‐5‐hydroxytryptamine (HT)‐labelled platelets. Ca²⁺ mobilization, P‐selectin expression, Annexin V binding and microparticle formation were determined by flow cytometry. P_2T receptor activation amplified ADP‐induced aggregation initiated by the P2Y₁ receptor, as well as amplifying aggregation, secretion and procoagulant responses induced by other agonists, including U46619, thrombin receptor‐activating peptide (TRAP) and collagen, independent of thromboxane A₂ synthesis, which played a more peripheral role. P_2T receptor activation sustained elevated cytosolic Ca²⁺ induced by other pathways. These studies indicate that the P_2T receptor plays a central role in amplifying platelet responses and demonstrate the clinical potential of P_2T receptor antagonists.