Cholinergic denervation of the rat hippocampus caused by electrolytic lesions of the medial septum (MS) results in a time-bound ingrowth of peripheral sympathetic noradrenergic fibers from the superior cervical ganglion to the dentate gyrus and CA3 region of the hippocampus. To determine the functional significance of hippocampal sympathetic ingrowth (HSI), [H-3]phorbol-12,13-dibutyrate (PDBu) binding was assessed 4 weeks after MS lesions. In control animals, affinity for [H-3]PDBu binding was found to be greater in the dorsal compared to ventral hippocampus, while the number of binding sites (B(max)) was similar between regions. Regardless of the presence of HSI, MS lesions resulted in increased affinity in the dorsal hippocampus, while the B(max) was found to 'normalize' in the ventral hippocampus by HSI. These results suggest that HSI is functional and can alter important cellular events.