The neuronal sprouting of noradrenergic fibers was studied in the hippocampal formation. The extent and time course of lesion-induced plasticity of both central and peripheral noradrenergic neurons was determined by assaying norepinephrine (NE) concentrations and high-affinity [3H]NE uptake in the dentate gyrus at 2 to 16 weeks after medial septal lesions. Two weeks after a medial septal lesion there was a dramatic decrease in dentate NE. During the subsequent weeks normal concentrations of dentate NE were reestablished. The recovery or increase of NE with time reflected a contribution from both central and peripheral noradrenergic systems. Although both central and peripheral noradrenergic systems contributed to this recovery, they did so in very different ways. The time course of the central noradrenergic response was slower than that of the peripheral system and the final NE concentrations were quite different for the two systems. The central adrenergic system's sprouting response apparently stabilized when normal NE concentrations were attained, whereas the ingrowth of peripheral sympathetic fibers continued to concentrations that were well above normal unoperated levels. The findings have implications in relationship to the different possible controlling mechanisms governing neuronal plasticity of the central and peripheral noradrenergic systems.