In order to assess the possible presence of presynaptic P2 receptors for nucleotides in the hippocampus, adenosine triphosphate and betagamma-methyleneATP have been examined on paired-pulse inhibition in rat hippocampal slices. Both compounds reproduced the effects of adenosine and reduced the amount of paired-pulse inhibition at an interpulse interval of 10 ms and increased the amount of facilitation at intervals of 20 and 50 ms. These effects were prevented by 8-phenyltheophylline and adenosine deaminase, indicating their mediation by adenosine. The effects were also reduced by suramin at 50 microM, suggesting the possible activation of P2 receptors. It is suggested that a population of P2 receptors may exist which promote the release of endogenous adenosine in the hippocampus.