Neonatal handling is known to induce long-lasting changes in behavioral and neuroendocrine responses to stress. Since the central noradrenergic system participates in the adaptive responses to stressful conditions we have analyzed the effects of postnatal handling on beta-adrenoceptor binding sites and isoprenaline- and forskolin-stimulated cyclic AMP accumulation in cerebral cortex, hippocampus and cerebellum of rats at 1 and 3 months of age. Handled animals showed reduced emotional reactivity and lower ACTH and corticosterone secretion after stress. Binding studies using [(3) H]CGP12-177 revealed increased beta-adrenoceptor binding sites in handled rats in cerebellum and cerebral cortex with no changes in hippocampus, and decreased affinity in all cerebral regions. Handling reduced basal levels of cyclic AMP in hippocampus and cerebellum but not in cerebral cortex. The concentration-response curves of cyclic AMP to isoprenaline were displaced to the right in cerebellum of handled rats without differences in Emax; however, Emax was significantly reduced in cerebral cortex and hippocampus. Direct stimulation of the catalytic subunit of adenylyl cyclase by forskolin reduced the efficiency in hippocampus and cerebellum, but not in cerebral cortex of handled animals. It is concluded that neonatal handling reduces the binding properties of beta-adrenoceptor and its primary biochemical responses in the young rat brain, which may account for the reduced responsiveness to stress attained in the handled rats, and may explain the persistence of the effect. The present study emphasizes the role of the central noradrenergic system in modulating the behavioral and neurendocrine responses to neonatal handling.