Peripheral noradrenergic fibers from the superior cervical ganglion (SCG) appear in the hippocampal formation of the adult rat central nervous system following damage to the medial septal nucleus or its afferent fibers. The appearance of these fibers coincides with a significant and substantial increase in the concentration of norepinephrine in the dentate gyrus and in the ability of synaptosomes made from the dentate to take up [3H]norepinephrine (NE) in vitro. Up to 7 weeks following a medial septal lesion, dentate norepinephrine levels are significantly lower if the sympathetic preganglionic trunk has been sectioned at the time septal lesions are made. By contrast, the uptake of [3H]NE into dentate synaptosomes is not affected by the preganglionic section. Furthermore, if the sectioned preganglionic trunk is allowed to reinnervate the SCG, the dentate NE concentration rapidly returns to levels equivalent to dentates with intact sympathetic preganglionic trunks. In addition to the ingrowth of the sympathetic fibers, central noradrenergic fibers display a sprouting or 'pruning' response to medial septal lesions. These data show that afferent input regulates the neurotransmitter concentration during sympathetic ingrowth while retrograde influences from the target appear to regulate the density or extent of the growing fibers. The experimental findings are discussed in light of the hypothesis that the hippocampal formation is capable of producing a sympathetic growth factor following septal denervation.