Effects of the cyclic AMP agonists 8-(4-chlorophenylthio)-adenosine 3':5' cyclic monophosphate (CPT-cAMP), dibutyryl cyclic AMP (dbcAMP) and forskolin were studied on extracellular field potentials in rat neocortex slices in vitro. CPT-cAMP and forskolin produced a prolonged enhancement of epileptiform activity resulting from removal of Mg2+ from the bathing medium. DbcAMP had no apparent effect except at high concentrations (1 mM), when it reduced bursting activity. Field potentials observed following electrical stimulation of the corpus callosum in the presence of Mg2+ were enhanced by CPT-cAMP and dbcAMP; however forskolin was without effect. Intracellular recording techniques demonstrated a transient excitatory influence of dbcAMP. The results indicate a role for cyclic AMP in seizure mechanisms.