The role of adenosine in regulating epileptiform discharge was studied in the in vitro hippocampal slice preparation. Exogenously applied adenosine appeared to have anticonvulsant properties (EC50 approximately 10 microM), in that it slowed or suppressed spontaneous interictal discharges. In addition, the release of adenosine (or related adenine nucleotides) from the slice preparation appeared to exert a tonic inhibitory influence on these types of discharges. This provides further evidence supporting a role for adenosine as an endogenous regulator of the excitability of the central nervous system, particularly in convulsive states.