Cyclic AMP generation was measured in isolated minces of the ipsilateral and contralateral cortex of young (3–4 months) and aged (28–29 months) Fischer-344 rats, 2 weeks after unilateral lesion of the nucleus locus ceruleus (LC). Measurements were conducted under basal conditions and in the presence of 0.1 mM isoproterenol. Despite marked norepinephrine (NE) depletion of about 90% in the ipsilateral cerebral cortex in both age-groups, cyclic AMP generation under basal conditions was unaffected. However, whereas isoproterenol-stimulated cyclic AMP generation was significantly higher in the NE-depleted ipsilateral cerebral cortex of young rats, such ‘denervation supersensitivity’ was not apparent in aged rats. Also, endogenous levels of NE were 31% higher, and isoproterenol-stimulated cyclic AMP generation was 33% lower in the contralateral ‘control’ cortex of aged rats than in young rats. These results suggest an age-related defect in the postsynaptic expression of noradrenergic mechanisms in the rat cerebral cortex. Further research using intermediate ages is needed to establish whether these age-related findings are caused by ‘senescence’ or are ‘develop