Neural afterdischarges generated in the presence of penicillin or low extracellular calcium concentrations were found to be inhibited by adenosine in the rat hippocampus in vitro. This anticonvulsant effect of adenosine is observed in the absence, as well as in the presence, of chemical synaptic transmission and apparently occurs at a postsynaptic site which is most sensitive in the apical dendritic region of the CA1 pyramidal cells. The methylxanthine theophylline antagonizes the effect of adenosine; and, the anticonvulsant action of thel-isomer of the adenosine analogue phenylisopropyladenosine (PIA) is substantially more potent than thed-isomer, findings which are characteristic of an A1 type adenosine receptor. The endogenous release of adenosine may therefore serve to tonically reduce the tendency for repetitive discharge in CA1 pyramidal cells via interaction with a high affinity A1 receptor which appears to be preferentially localized in the apical dendrites.