Convulsant doses of pentylenetetrazol (100 mg/kg) increase levels of both cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP in mouse cerebral cortex and hippocampus. In animals pretreated with reserpine, propranolol, or aminophylline, pentylenetetrazol seizures were more severe, cyclic AMP elevations were attenuated or blocked, and cyclic GMP increases were unaffected or augmented. These data indicate that norepinephrine, adenosine, and perhaps other biogenic amines have a regulatory effect on cyclic AMP, but not cyclic GMP, levels in epileptic brain. An increased level of cyclic AMP in brain tissue may have an antiepileptic effect leading to seizure attenuation or termination. By contrast, elevated levels of cyclic GMP may have an epileptogenic effect in initiating or maintaining seizure activity.