Norepinephrine concentrations and tyrosine hydroxylase activity were determined in the brains of moderate-seizure and severe-seizure genetically epilepsy-prone rats (GEPRs) and in nonepileptic control rats. Both moderate-seizure (GEPR-3) and severe-seizure (GEPR-9) animals had widespread abnormalities in brain norepinephrine concentrations. Abnormalities in tyrosine hydroxylase activity were restricted to the midbrain. The state of abnormal seizure susceptibility, but not severity, in the GEPR may be determined by noradrenergic deficits in the hypothalamus/thalamus. Both seizure severity and susceptibility may be determined by noradrenergic deficits in the telencephalon, midbrain, and pons-medulla. Seizure severity but not susceptibility may be determined by noradrenergic abnormalities in the cerebellum.