The effects of ciliary neurotrophic factor on nitric oxide (NO)-induced cytotoxicity were examined in primary cultures of rat hippocampal neurons. The neurotoxicity was induced by NO donors, such as sodium nitroprusside (SNP), s-nitroso-N-acetylpenicillamine (SNAP), NOS substrate, L-arginine (L-Arg) and ionomycin (a calcium ionophore). Preincubation of the cultures with ciliary neurotrophic factor (CNTF) for 24 h promoted neuronal survival and decreased the LDH efflux and the level of NO induced by ionomycin. The protective effects of CNTF against NO cytotoxicity were concentration-dependent. The above findings suggest that CNTF promotes the survival of neurons in the hippocampus by preventing NO mediated neurotoxicity.