This study investigated the effect of NO on c-Fos expression using immunocytochemical techniques, following training in the one-trial passive avoidance response and Morris water maze tasks. Fos-like immunoreactive (FLI) neurons were examined in the hippocampus and cerebral cortex of rats in which intracerebroventricular (i.c.v.) injection of Nomega-nitro-L-arginine (NAME) was given 30 min before training in the experimental groups. The results showed that: (1) when compared with untreated rats or rats receiving i.c.v. saline injection, fos-like immunoreactive neurons were significantly increased in both brain regions following training in either task, and (2) preceding i.c.v. injections of NAME blocked both the formation of memory and the increased expression of c-Fos in both brain regions subjected to training on the two models. These results suggest that NO production may be a critical factor for the formation of memory and the enhanced c-Fos expression, and so might contribute to the long-term plasticity of synaptic organization in the two brain regions.