Acute and chronic nicotine treatment has been found to improve learning and memory function in a variety of tasks. In several studies we have found that chronic nicotine infusion improves working memory performance. Replicating these results, the current study showed that chronic nicotine treatment (12mg/kg/day) significantly improved working memory performance in the radial-arm maze. The nicotine effect did not diminish during the 2 weeks following withdrawal. The nicotine-induced improvement was eliminated when the nicotinic antagonist mecamylamine (3mg/kg/day) was given concurrently, suggesting that the nicotine effect was mediated via actions on the nicotinic receptor. Surprisingly, when this chronic dose of mecamylamine was given alone, it caused a transient improvement in choice accuracy during the first week of administration. This improvement subsequently became attenuated and was not evident at all by the third and fourth weeks of administration.