The P2X7-receptor is a member of ATP-gated non-specific cation channels which is unique in possessing an extra long C-terminal domain. The functional expression and kinetics of activation and deactivation of P2X7 receptors expressed in Xenopus oocytes were investigated by means of the two microelectrode voltage clamp method. The activation by ATP was best described by the sum of a monoexponentially and a linearly increasing component. The deactivation was best approximated by the sum of two exponentially declining terms. The concentration-response analysis of the wild type P2X7 receptor revealed two ATP activation sites at about 10 and 500 mM ATP ^4-. The deletion of the C-terminal domain drastically reduced the amplitude of the P2X7-dependent ionic currents, abolished the effect of the low affinity component and resulted in monoexponential activation and deactivation time courses. Substitution of the cut C-terminal domain by supplementary expression of the C-terminus together with the truncated channel completely restored the amplitude and the kinetics of the wild type receptor. Shorter C-terminal domains only partially restore the maximal current amplitude but retain the kinetics of the truncated receptor. Other members of the P2X family which do not possess the long C-terminal domain are not influenced by supplementary expression of the C-terminus. We conclude that the C-terminal domain acts as a modulator of the P2X7 receptor kinetics.