beta-Adrenergic control of ornithine decarboxylase (ODC) activity is exerted only during a critical period in central nervous system development, playing an important role in neurotransmitter modulation of cell replication and differentiation. The current study examines the effects of lesions caused by 6-hydroxydopamine administration to neonatal rats, or of gestational exposure to propranolol, on the subsequent development of the ODC response to beta-adrenergic stimulation elicited by an acute intracisternal challenge with isoproterenol. 6-Hydroxydopamine treatment severely attenuated the ability of isoproterenol to stimulate ODC in the cerebellum, a tissue that shows a postnatal peak of ODC reactivity. In contrast, much smaller effects were seen in the cerebral cortex, which has an earlier (pre/perinatal) peak of ODC, despite the fact that norepinephrine depletion was more persistent in the cortex. On the other hand, blockade of fetal beta-receptors by maternal propranolol infusions resulted in immediate postnatal attenuation of the ODC response in cerebral cortex, but not cerebellum. These data suggest that early exposure of beta-receptors to norepinephrine "programs" the subsequent efficiency of the receptor linkage to ODC during a critical ontogenetic period that occurs prenatally in the cerebral cortex and postnatally in the cerebellum.