Nerve growth factor (NGF) has been postulated to play an important role in the process of sympathetic sprouting into the septally deafferented hippocampal formation. In the current investigation we have used transplants of NGF-dependent neonatal superior cervical ganglion (SCG) neurons to investigate the influence of NGF and septal denervation (either alone or in combination with one another) upon neuronal survival and intrahippocampal sprouting. In the current model, SCG transplants were placed onto the dorsal surface of the CA1 hippocampal subfield and a continuous infusion device was used to deliver either NGF or vehicle into the hippocampal parenchyma. Following 15 days of vehicle infusion, little or no sympathetic neuronal survival was observed and no hippocampal fiber outgrowth was detected. NGF infusions, however, promoted both neuronal survival and intrahippocampal fiber outgrowth directed mainly toward the location of the infusion cannula. Septal denervation, achieved by either a septal ablation or fimbria-fornix transection, had no discernible impact upon SCG neuronal survival or fiber outgrowth, with or without NGF infusions. Similar results were also obtained when SCG were transplanted directly within the cortex, with or without an intracortical infusion. It appears, therefore, that NGF may be a sufficient, as well as necessary, component for eliciting and guiding the invasion of a tissue by NGF-sensitive fibers.