We have used a microdialysis technique to analyze the effects of nicotine administration on the release of dopamine in the striatum and the nucleus accumbens (NAC) in rats under footshock stress. In the striatum, neither chronic systemic nicotine administration alone nor stress alone changed the extent of dopamine release. During stress application, however, chronic nicotine administration significantly increased dopamine release. In the NAC, stress did not induce increase in dopamine release in rats given nicotine chronically. However, in rats subjected to stress alone, dopamine release in the NAC was significantly increased after stress. In the striatum, the local infusion of 1.0 mM nicotine increased dopamine release. Furthermore, stress significantly increased nicotine-induced dopamine release. The local infusion of 1.0 mM nicotine into the NAC significantly increased dopamine release, but the levels returned to the baseline 30 min later. On the other hand, stress alone induced the release of dopamine 30 min later and the combination of stress and nicotine induced the release of dopamine during the stress and the effects lasted for 30 min. These results suggest that the responses of nicotine-induced dopamine release were different in the striatum and in the NAC under the stress. Stress and nicotine (systematically or locally administered) induced an immediate effect on dopamine release in the striatum, but in the nucleus accumbens stress alone and the combination of stress and nicotine induced a lasting release of dopamine (DA).