Cigarette smoking has been known to suppress both 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP)-inducible parkinsonism in rodents and idiophatic Parkinson's disease in humans. However, the precise mechanism underlying the possible protective effect of smoking is not clearly elucidated. In order to show the protective action of smoking, we investigated the inhibitory effect of cigarette smoke components on brain mitochondrial monoamine oxidase B (MAO-B) which converts MPTP into its toxic metabolites. Smoke constituents were isolated from cigarette smoke condensate (CSC) through solvent extraction and silica gel chromatography, and identified by GC-MS. In total 48 eligible constituents including nicotine and its metabolites were selected, and their inhibitory effects on MAO-B were determined. Phenolic compounds such as hydroquinone, methylcatechol, indols, and farnesol strongly suppressed MAO-B activity in vitro in dose dependent manner, whereas, dibutylphthalate, vanilline, dimethylamine, and diphenylamine had a slight effect. Among tobacco alkaloids, only myosmin had an inhibitory effect on the enzyme. These results suggest that such action of cigarette smoke may be closely related to the suppression of MPTP-neurotoxicity and the lesser incidence of Parkinson's disease in smokers than in nonsmokers.