A nicotine agonist, ¹¹C-labeled (S)-nicotine, was synthesized by N-methylation of (S)-nornicotine with [¹¹C]-methyl iodide in dimethylformamide-dimethylsulfoxide in order to study nicotinic receptors in the human brain by positron emission tomography. The radiochemical yield of this N-methylation reaction was more than 90% within 5 min. After purification by high performance liquid chromatography the radiochemical purity of the product was more than 99% and the specific radioactivity was 7.4-11.1 GBq/μmol. The regional distribution of (S)-[¹¹C]nicotine in the mouse brain after intravenous injection was compared with that of (R)-[¹¹C]nicotine. After injection of (S)-[¹¹C]nicotine, the regional uptake of radioactivity was in the following order : cortex > thalamu≈hippocampus>striatum>hypothalamus>cerebellum. Moreover, (S)-[¹¹C]nicotine was displaced from the brain by unlaceled (S)-nicotine, but unlabeled (R)-nicotine caused no change in uptake. In contrast, (R)-[¹¹C]nicotine showed a lower brain uptake and lesser regional differences in radioactivity.