Objective: The authors' goal was to study presynaptic dopamine activity in smoking and nonsmoking human subjects in vivo. Method: [F-18]Fluorodopa ([F-18]DOPA) uptake K-i values in the basal ganglia of nine smoking and 10 nonsmoking healthy men were measured with positron emission tomography Results: Significantly higher [F-18]DOPA uptake was observed in both the putamen (average 17.3% higher) and the caudate (average 30.4% higher) of smokers than in those of nonsmokers. Conclusions: Smoking is related to greater dopamine activity in the human basal ganglia. Nicotine-induced dopamine activity may be a relevant mechanism in dependence on cigarette smoking.