EXTRACELLULAR ATP exerts its effects through P-2 purinoceptors(1) : these are ligand-gated ion channels (P-2X)(2,3) or G-protein-coupled receptors (P-2Y, P-2U)(4). ATP at P-2X receptors mediates synaptic transmission between neurons(5-7) and from neurons to smooth muscle(1), being responsible, for example, for sympathetic vasoconstriction in small arteries and arterioles(8,9) We have now cloned a complementary DNA encoding the P-2X receptor from rat vas deferens and expressed it in Xenopus oocytes and mammalian cells. ATP activates a cation-selective ion channel with relatively high calcium permeability. Structural predictions suggest that the protein (399 amino acids long) is mostly extracellular and contains only two transmembrane domains plus a pore-forming motif which resembles that of potassium channels. The P-2X receptor thus defines a new family of ligand-gated ion channels.