1. Characterization of P2X receptors on neurons of guinea-pig superior cervical ganglion (SCG) has been carried out using a whole-cell voltage-clamp technique. 2. Application of ATP and alpha,beta-methylene ATP (alphabeta-MeATP) produced fast activating inward currents, which desensitized slowly. The maximum response to alphabeta-MeATP was 36 +/- 23 % (range 0.1-100 %) of that evoked by ATP in the same cell. 3. Co-application of alphabeta-MeATP (300 microM) with ATP (300 microM) produced a response that was 97 +/- 1 % of that given by ATP alone. Following desensitization with alphabeta-MeATP, the decrease in response to ATP was equal to the absolute reduction in response to alphabeta-MeATP in the same cell. 4. The concentration-response curve for alphabeta-MeATP had an EC50 of 42 microM and a Hill coefficient of 1.17. For cells where the ratio of alphabeta-MeATP/ATP currents at 100 microM was < 0.1, the ATP concentration-response curve had an EC50 of 56 microM and a Hill coefficient of 1.95. However, in cells where the ratio was > 0.7, the curve had an EC50 of 60 microM and a Hill coefficient of 0.97. 5. The response to 100 microM alphabeta-MeATP was inhibited by 2' (or 3')-O-trinitrophenyl-ATP (TNP-ATP) with an IC50 of 70 nM. However, on cells where the ratio of alphabeta-MeATP/ATP currents was < 0.1, ATP was inhibited by TNP-ATP with an IC50 of 522 nM. 6. Immunohistochemical staining with antibodies raised against rat P2X2 and P2X3 epitopes suggested that both subunits were expressed by guinea-pig SCG neurons. 7. We conclude that varying proportions of two distinct P2X receptors coexist on the cell bodies of individual guinea-pig SCG neurons, which may correspond to homomeric P2X2 and heteromeric P2X2/3 receptors.