The thrombin receptor is a G protein-coupled receptor, but the G proteins functionally coupled to this receptor in human platelets are not yet definitively identified. Thrombin stimulation of platelets leads to phospholipase C-mediated increases in intracellular calcium, and previous studies have suggested that the thrombin receptor is coupled to members of the G q family. We now demonstrate direct GTPase activation by thrombin receptor activation peptide (TRAP) in human platelet membranes, and specific inhibition of TRAP-activated GTPase by antibodies to G q . These data demonstrate functional coupling of the thrombin receptor to a member of the G q family.