Rats received a unilateral lesion of the nucleus basalis magnocellularis (NBM) by infusion of ibotenic acid. Starting 2 weeks after the lesion, the animals were treated with nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) by intraparenchymal infusion of 3 micrograms per day for 4 weeks. Lesioned control animals received a similar amount of cytochrome c. The activity of choline acetyltransferase (ChAT) in the frontal neocortex was significantly reduced by the lesion (-39%). However, the intraparenchymal treatment with NGF or BDNF did not affect cortical ChAT activity. The number of p75 NGF receptor-immunoreactive neurons in the NBM was significantly decreased (-49%) by the lesion and was not affected by NGF or BDNF. The size of the remaining neurons was significantly increased by NGF (+32%), but not by BDNF (+12%). Similarly, in situ hybridization showed enhanced expression of the p75 NGF receptor following treatment with NGF, but not with BDNF. These results suggest that although BDNF occurs in the target area of cholinergic NBM neurons, its effects on these neurons are less pronounced than those of NGF.