Transection of the adult rat dorsal fornix and fimbria (F-F) induced a sensitivity of the cholinergic neurons in the medial septum and diagonal band (MS/DB) to exogenous mouse nerve growth factor (mNGF). Continuous infusion of mNGF for two weeks after complete unilateral F-F aspiration resulted in a stimulation of choline acetyltransferase (ChAT)-specific activity in precise micro-dissections of the MS/DB ipsilateral to the transection to a level that was 200% higher than that measured in normal adult animals. This supranormal stimulation of ChAT activity reached plateau levels after 10 days of NGF infusion and was dose-dependent with an E.D.50 equal to 120 ng/day. Administration of mNGF had no effect on the ChAT activity in the MS/DB of normal animals or animals with a unilateral transection of only the supracallosal dorsal septo-hippocampal pathway. Partial transection experiments indicated that a predominent pathway for cholinergic neurons potentially sensitive to exogenous mNGF runs in the paramedian F-F. Administration of mNGF also induced a stimulation of ChAT activity in dissections of the caudate-putamen both ipsi- and contralateral to the infusion cannula. This indicates that unlike the cholinergic projection neurons of the MS/DB, adult cholinergic striatal interneurons are sensitive to exogenous NGF without prior axotomy.