Genetically epilepsy-prone rats (GEPR-9) and kindled rats have reduced noradrenergic function. In the present study, norepinephrine-stimulated accumulation of inositol phosphates was reduced in cerebral cortex of GEPR-9 and kindled rats when compared to control and non-kindled rats, respectively. No such reduction was found in amygdala/pyriform cortex and hippocampus. These results support the hypothesis that cortical noradrenergic and associated second messenger systems are impaired in epilepsy.