Damage to the rat septohippocampal pathway results in the growth of sympathetic axons from nearby blood vessels into the denervated hippocampal formation. Sympathohippocampal sprouting exhibits lesion specificity--that is, only injury to the septohippocampal projection elicits the sprouting response. Whether other perivascular fibers sprout in response to septohippocampal injury (response specificity) has been addressed in the present study. Using cathecholamine histofluorescence and acetylcholinesterase histochemical techniques, we determined the distribution and incidence of perivascular sympathetic and nonsympathetic fibers associated with parahippocampal blood vessels in normal rats and in rats sustaining medial septal lesions. We found that sympathetic fibers are more numerous than acetylcholinesterase-positive fibers at all septotemporal levels of the hippocampal formation and that both types are very rare at dorsal hippocampal levels in normal rats. Following medial septal lesions, however, there is a tremendous increase in the number of perivascular sympathetic fibers at dorsal hippocampal levels but no change in the number of acetylcholinesterase-positive fibers. Electron microscopic observations indicate that the increase in perivascular fibers is due to increases in the number of sympathetic axonal fascicles as well as the number of axons per fascicle. Furthermore, both light and electron microscopic data suggest that parahippocampal veins are normally not accompanied by perivascular fibers but are associated with sympathetic fibers following medial septal lesions. These results indicate that sympathetic sprouting in response to septohippocampal denervation exhibits specificity not only in terms of the lesion which elicits such sprouting but also in terms of the types of fibers that respond to the lesion.