The effects of adenosine 5'-triphosphate (ATP) on voltage-clamped and dissociated rat hippocampal neurons was investigated. Over 30% of neurons possessed ATP-activated inward currents at a holding potential of -70 mV. The ED50 for these currents was 150 μM. At this concentration they were blocked by suramin (1 mM), indicating the involvement of P2-purinoceptors. The P2 purinoceptor agonist potency was 2-methylthio ATP > ATP > ADP > α,β-methylene ATP, thus identifying these purinoceptors as belonging to the P2x subclass. The reversal potential for the ATP-activated currents was -45 ± 8 mV. Ion substitution experiments showed that the permeability ratio for K+/Na+/Cs+/Cl-, was 18:3:2:1, according to the Goldman-Hodgkin-Katz equation, so that ATP activates cationic and anionic conductances in hippocampal neurons.