Intracerebral administration of 6-hydroxydopamine (6-HDA) along the dorsal noradrenergic bundle produced a gradual and long-lasting decrease of norepinephrine (NE) in hippocampus. This decrease in NE levels initially was accompanied by a parallel decrease in the activity of the rate-limiting enzyme for NE biosynthesis, tyrosine hydroxylase (TH). However, by 14 days the decrease in enzyme activity was much less pronounced than that of NE levels, resulting in an 8-fold increase in the ratio of TH activity to NE content. This persisted for at least two months, the longest time examined. Depletion of NE and changes in TH activity were not observed in cerebellum after the 6-HDA treatment. The selective increase in the ratio of TH activity within denervated regions may reflect an adaptation to the lesion whereby residual noradrenergic neurons increase their synthesis and release of NE.