Unilateral stereotaxic fimbrial transection was used to disrupt the cholinergic pathway from the medial septum to the hippocampus in adult rats. The resulting alterations in hippocampal nerve growth factor (NGF) and mRNANGF levels were then analysed by two-site enzyme immunoassay and quantitative Northern blots, respectively. NGF levels did not change up to one week after lesion but had increased to 145% of contralateral control values by two weeks. In contrast, mRNANGF levels were not changed at this time point. Neither bilateral fimbrial transection, nor removal of the sympathetic innervation of hippocampal vasculature by excision of the superior cervical ganglia, led to more pronounced increases in NGF levels. These results are consistent with the concept that the magnocellular cholinergic neurons in the medial septum are constantly reducing hippocampal NGF levels by retrograde axonal transport.