OBJECTIVE: The authors’ goal was to study presynaptic dopamine activity in smoking and nonsmoking human subjects in vivo. METHOD: [18F]Fluorodopa ([18F]DOPA) uptake Ki values in the basal ganglia of nine smoking and 10 nonsmoking healthy men were measured with positron emission tomography. RESULTS: Significantly higher [18F]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.