This study reports an investigation of smokers and non-smokers performed in order to determine differences in the olfactory perception of the stereoisomers of nicotine; 38 subjects participated (20 smokers, 18 non-smokers). The investigated parameters were: hedonic ratings and intensity estimates, discrimination between enantiomers, estimates of detection thresholds and the odorous quality of nicotine enantiomers. Subjects were able to discriminate between the two stereoisomers of nicotine. Whereas both groups reported the R(+) isomere to cause an unpleasant sensation, the S(-) isomere was perceived as pleasant by smokers, but not by non-smokers. The differences in the hedonic ratings of S(-) nicotine between smokers and non-smokers might be due to the smokers' experience of the pharmacological action of S(-) nicotine, which is the main isomere in cigarette smoke.