The effects of endogenously released adenosine on the excitability of hippocampal neurons were studied using the novel and highly selective adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Extra- and intracellular recordings performed in area CA1 and CA3 of the guinea pig hippocampal slice preparation revealed that a transient suppression of an inhibitory purinergic tonus by DPCPX leads to sustained interictal-like epileptiform activity arising in area CA3. Once induced, the spontaneous burst discharges were apparently irreversible within the observation period, even after prolonged washout (2-3 h) in normal solution. In contrast, the hyperpolarizing action of exogenous adenosine, which was substantially reduced by DPCPX, recovered within 30-60 min of drug washout, indicating that DPCPX was not irreversibly bound to the A1-receptor.