Cation-selective P2X receptor channels were first described in sensory neurons(1-4) where they are important for primary afferent neurotransmission and nociception(5,6). Here we report the cloning of a complementary DNA (P2X(3)) from rat dorsal root ganglia that had properties dissimilar to those of sensory neurons. We also found RNA for (P2X(1)) (ref. 7), (P2X(2)) (ref. 8) and P2X(4) (ref. 9) in sensory neurons; channels expressed from individual cDNAs did not reproduce those of sensory ganglia. Coexpression of P2X(3) with P2X(2), but not other combinations, yielded ATP-activated currents that closely resembled those in sensory neurons. These properties could not be accounted for by addition of the two sets of channels, indicating that a new channel had formed by subunit heteropolymerization. Although in some tissues responses to ATP can be accounted for by homomeric channels(1,7-10), our results indicate that ATP-gated channels of sensory neurons may form by a specific heteropolymerization of P2X receptor subunits.