Substance P and selective neurokinin receptor agonists have been tested for their ability to induce shape change in rabbit platelets. Substance P and the NK 1 receptor agonist Ac [Arg 6 ,Sar 9 ,Met(O 2 ) 1 1 ]-substance P (6-11) induced shape change (EC 5 0 = 3 and 6 nM, respectively), whereas the selective NK 2 agonist [Nle 1 0 ]-Neurokinin A (4-10) and the selective NK 3 agonist [MePhe 7 ]-Neurokinin B did not show any effect. Moreover, the specific NK 1 receptor antagonist CP-96,345 selectively and dose-dependently counteracted the effect of substance P or of the NK 1 receptor agonist (IC 5 0 = 2 and 0.8 nM, respectively), whereas the selective NK 2 receptor antagonist, SR 48968, had no effect. Unlike for serotonin or low doses of ADP, epinephrine did not allow substance P or the NK 1 receptor agonist to become a proaggregating substance. These data therefore show that the NK 1 receptor is solely involved in the neurokinin-induced shape change of rabbit platelets.