The aim of this study was to investigate in smokers and nonsmokers (1) the olfactory and trigeminal detection of R(+)- and S(-)-nicotine and (2) the discrimination ability and hedonic estimation of nicotine enantiomers in olfactory and trigeminal concentrations. Thirty healthy male subjects (15 smokers, 15 nonsmokers) participated in the experiments. A randomized sequence of R(+)- and S(-)-nicotine stimuli (seven R(+)- and seven S(-)-nicotine stimuli) were introduced into the right nostril of the subjects using a Kobal-olfactometer. The subjects were instructed to group the stimuli into two categories (A and B). To test the role of the olfactory and the trigeminal system in this discrimination task, the authors studied the olfactory detection threshold for the 'odorous' sensation and the trigeminal detection thresholds for the 'burning' and 'stinging' sensations. Nicotine enantiomers were presented at the individual 'olfactory' and 'trigeminaI' concentration levels. The subjects estimated the hedonic properties using a bipolar visual analog scale (from 'very unpleasant' to 'very pleasant'). A statistical evaluation (t-test) revealed that the subjects were able to identify R(+)- and S(-)-nicotine at olfactory and trigeminal concentrations (p ≤ 0.01, p ≤ 0.001, respectively). At concentrations near the detection thresholds, i.e., clearly below subjective pain thresholds, smokers rated both nicotine stereoisomers to be significantly more pleasant than did nonsmokers (t-test, R(+)-nicotine:p ≤ 0.05; S(-)-nicotine: p ≤ 0.01). Increasing the concentrations to above trigeminal thresholds resulted in a difference in hedonic estimates. Smokers perceived the S(-)-isomer as being less unpleasant than nonsmokers at trigeminal concentrations (t-test, p ≤ 0.001). This difference in perception might be explained by the smokers' experience with S(-)-nicotine, which is the natural nicotine enantiomer in tobacco.