The action of ciliary neurotrophic factor (CNTF) on intercellular free Ca2+ concentrations [Ca2+]i induced by glutamate (Glu) in primary cultured hippocampal neurons were detected with Fura2/AM, a Ca2+-sensitive fluorophore, and the morphological influence of G-protein on it was objected. Glu could induce rapid increase of [Ca2+]i in hippocampal neurons. CNTF had no significant action on [Ca2+]i in resting hippocampal neurons. However, after incubation of CNTF for 5 min, the increase of [Ca2+]i in hippocampal neurons rapidly induced by Glu was inhibited. Pretussis toxin (PTX)-sensitive G protein could block the action. These results indicate that a new non-genomic rapid sideway might exist in the upper stream of CNTF signal transduction pathway, which was related to Ca2+ signal transduction.