Basal forebrain cholinergic neurons respond to nerve growth factor (NGF), and it has been suggested that the administration of NGF might prevent their degereration in patients with Alzheimer's disease. One major prerequisite to be fulfilled before the consideration of clinical trials of NGF in patients with Alzheimer's disease is the demonstration that human NGF affects basal forebrain cholinergic neurons in primates. In the present study, we used a recombunant human nerve growth facotr (rhNGF), which we previousl showed to be active on rat basa forebrain cholinergic neurons, in nonhuman primates with a unilateral transection of the fornix (a well-established model for the induction of retrograde degenerative changes in septal cholinergic neurons). After the lesion, one group of animals received rhNGF and a second group received vehicle solution for 2 weeks. In animals receiving vehicle, the medical septal nucleus ipsilateral to the lesion showed reductions in numbers (55°) and size of cell bodies immunoreactive for NGF receptor and choline acetyltransferase. In Sissl stains, many cells showed frduced size and basophilia. The rhNGF completely prevented alternation in the number and size of NGF receptor—and choline acetyltransferase—immunnoreactive neurons in the medical septal nucles and reversed atrophy in a subpopulation of large, basophilic medical which we have previously used in the same primate lesion paradigm. The restoration of the phenotype of injured acetylcholine-dependent memory impariments that occur in aged nonhuman primates. In concert, results of the present investigation provide critical information for the futrue use of NGF in in patients with neurological disorders that affect NGF-responsive cells in the peripherl and central nervous system.