Damage to septohippocampal neurons in the adult rat results in sprouting of sympathetic axons into the denervated hippocampal formation. However, the distribution of sympathohippocampal fibers has only been assessed with light microscopic techniques, and it is not known if the sprouted fibers leave the blood vessels, along which they migrate into the hippocampal formation, to enter the hippocampal neuropil and, if they do, whether they form synaptic contacts with central neurons. Using the tetramethylbenzidine technique to visualize anterogradely transported wheat germ agglutinin-horseradish peroxidase conjugate, we identified sprouted sympathetic fibers in the hippocampal formation at both the light and electron microscopic level in albino rats receiving medial septal lesions. The majority of labeled fibers were observed within the regions immediately above and below the granule cell layer. Although most of the labeled sprouts were observed in association with intraparenchymal blood vessels, where they were usually apposed to the basal lamina, approximately a third of the labeled profiles were present within the neuropil with no obvious vascular relationships. Most of the profiles were identified as unmyelinated axons or vesicle-filled varicosities. Many of the latter structures contained small dense-cored vesicles, but in our sample none of the labeled profiles were observed to form membrane specializations with adjacent structures, and many were partly surrounded by presumed astrocytic processes. These results document the invasion of the CNS by sprouting axons of peripheral origin indicating that axonal elongation from uninjured neurons can occur within the mature mammalian CNS under certain circumstances. In addition, the presence of significant numbers of sympathetic fibers within the hippocampal neuropil indicates that they may be in a strategic position to influence hippocampal function.