It has been postulated that addiction to nicotine is mediated by dopamine release in the mesolimbic system. It is possible that nicotine might act directly on the dopamine terminals to release dopamine. This hypothesis was tested by infusing nicotine through a microdialysis probe into the nucleus accumbens of freely moving rats. Dopamine, dihydroxyphenylacetic acid, and homovanillic acid from the extracellular space were collected by microdialysis and measured by high pressure liquid chromatography. Nicotine increased extracellular dopamine in a dose-related manner. Systemic injection of the nicotine antagonist mecamylamine blocked the dopamine increase induced by local nicotine. These results suggest that nicotine releases dopamine by a local action in the nucleus accumbens terminal area of the mesolimbic system. Presynaptic induction of dopamine release might play a role in nicotine addiction.