Nerve growth factor is required for the survival and maintenance of cholinergic neurons in the central nervous system. The direct infusion into the rat's septum of an anti-nerve growth factor monoclonal antibody, which inhibits nerve growth factor bioactivity seven times more strongly than a polyclonal antibody, caused very severe damage to the hippocampal cholinergic system. Anti-nerve growth factor polyclonal antibody also neutralized endogenously occurring nerve growth factor. The infusion of anti-nerve growth factor polyclonal antibody produced a dysfunction of memory and decreased choline acetyltransferase activity and acetylcholinesterase staining in the hippocampus. The cholinergic dysfunction and impairment of memory recovered to the normal level two weeks after cessation of the infusion of the anti-nerve growth factor polyclonal antibody. These results suggest that a deficit of nerve growth factor in the adult brain causes neuronal dysfunction.