Neonatal 6-hydroxydopamine treatment was used to destroy the noradrenergic nerve terminals in rat cerebral cortex and thus give some insight into the in vivo regulation of alpha-adrenoceptor subtypes, which in turn provides information concerning the anatomical localization of alpha 1- and alpha 2-adrenoceptors. Treatment of rats in the neonatal period with 6-OHDA causes an irreversible decrease in noradrenaline levels of the cerebral cortex compared to controls. Differences in [3H]clonidine and [3H]prazosin binding in the cerebral cortex occurred which varied depending upon the time elapsed between denervation and the binding assay. In rats aged 7-14 days there was a 20% decrease in the number of alpha 2-adrenoceptors and a slight increase in alpha 1-adrenoceptors. In older rats (45-50 day old) both types of alpha adrenoceptors were increased. Results of this study indicate that alpha 2-adrenoceptors located on presynaptic noradrenergic terminals represent only a small proportion of the total alpha 2-adrenoceptors in rat cerebral cortex. Increases in the binding capacity after 67-OHDA treatment indicate an up-regulation phenomenon affecting alpha 1-adrenoceptors and alpha 2-adrenoceptors located on structures other than noradrenergic nerve endings.