In the present study, the influence of direct intrahippocampal injection of NGF (nerve growth factor) on synaptosomal free [Ca2+]i in 1-month-old and 18-month-old mice was observed. The regulation of NGF on synaptosomal free [Ca2+]i in vitro was also investigated. The synaptosomal free [Ca2+]i in the main brain regions (cerebral cortex, hippocampus, cerebellum, diencephalon) of these mice was measured by fluorescent probe Fura-2 of Ca2+ indicator and an AR-CM-MIC cation measurement system. The results are as follows: (1) NGF showed no detectable effect on hippocampal intrasynaptosomal free [Ca2+]i in 1-month-old mice, but appropriate dose of NGF was shown to markedly reduce [Ca2+]i in 18-month-old mice. (2) Under the condition of low [Ca2+]i level caused by the drug, NGF was found to increase [Ca2+]i; conversely, was reduced [Ca2+]i when intracellular Ca2+ was overloaded. These results suggest that NGF has dual regulation on Ca2+ level in brain and this might be an important mechanism for its action in improving memory lesion, in aged person.