Adenosine 5 triphosphate (ATP) is copackaged in exocytotic granules and secreted with a number of neurotransmitters and local mediators from many cell types (Whittaker, 1982). Indeed, the exocytosis of ATP evokes fast synaptic potentials in the central and peripheral nervous system (Edwards, Gibb & Colquhoun, 1992; Evans, Derkach & Surprenant, 1992; Silinsky, Gerzanich & Vauner, 1992). ATP can also be released from the cell cytosol via nonsynaptic mechanisms, for example by diffusion after sudden rupture of intact cells by tissue injury. Moreover, cytosolic ATP can be translocated to the extracellular medium by active transporters under hypoxic conditions (Clemens & Forrester, 1981; Forrester & Williams, 1977). Extracellular ATP exerts its diverse effects by binding to membrane proteins termed P2 receptors (Dubyak & El-Moatassim, 1993). P2 receptors have been classified in two families according to amino acid sequence homology and transduction mechanisms:(i) a P2X family consisting of ligand-gated channels, of which seven subunits have been cloned (P2X1–7)(Buell, Collo & Rassendren, 1996b) and,(ii) a P2Y family consisting of G-protein coupled receptors with eight reported members (P2Y1–8)(Burnstock, 1996; Burnstock & King, 1996). Studies on native P2 receptors defined an additional class represented by the P2Z receptor. Its activation leads to the opening of large-conductance nonselective pores which results in cell lysis (Tatham & Landau, 1990). However, heterologously expressed P2X7 receptor presents functional properties that strongly resembles the behavior of native P2Z receptor (Surprenant et al., 1996a). The characterization of cloned P2X receptors constitutes a basic framework for a precise description of their physiological function. The aim of this review is to summarize recent advances in the cloning, functional characterization and tissue distribution of the P2X receptor subunits.