OBJECTIVE The interaction of sensory physiology and sleep has been studied for various sensory systems. Nevertheless, the question whether chemosensory (especially olfactory) stimuli may lead to arousals during sleep remains under discussion. Specifically, the central processing of olfactory information shows fundamental differences compared to other sensory systems. METHODS Prospective controlled trial. METHODS Sleep research facility, University Hospital. METHODS Five young healthy, normosmic volunteers. METHODS Intranasal chemosensory stimulation during sleep was based on air-dilution olfactometry. For olfactory stimulation H2S (smell of rotten eggs) was used in 4 concentrations (1, 2, 4, and 8 ppm). For trigeminal stimulation CO2 (stinging sensation) was also administered in 4 concentrations (10%, 20%, 40%, and 60% v/v) while odorless stimuli were used for control. METHODS Arousal reactions due to chemosensory stimulation were assessed during overnight polysomnography 30 seconds after the presentation of every stimulus during 23 nights of testing. RESULTS For olfactory testing, an average number of 703 olfactory stimuli and 157 odorless controls were used for analysis per subject. Even the highest stimulus concentration did not produce an increase in arousal frequency. For trigeminal testing, an average number of 405 stimuli and 79 controls were used for analysis per subject, and an increase in arousal frequency was observed following the increase of stimulus concentration. CONCLUSIONS With the present results we were able to demonstrate that, in contrast to trigeminal stimulation, the presentation of a strong but selective olfactory stimulus does not lead to arousals during nocturnal sleep in humans.