BACKGROUND: Bispectral index (BIS) has been designed to measure objectively the degree of sedation and hypnosis for several anesthetics. It is predicted that sedation and hypnosis during nitrous oxide inhalation affect BIS in an unusual manner due to a different mechanism compared to usual hypnotics. The aim of this study was to evaluate the effect of different concentration of nitrous oxide inhalation on BIS and sedation score. METHODS: Forty unpremedicated ASA physical status I or II patients scheduled for lower extremity surgery were studied. After performing epidural anesthesia, patients inhaled gradually increasing concentrations of nitrous oxide from 0 to 67% (15 minutes for each concentration) via a tightly sealed face mask. At the end of each inhalation, BIS and OAA/S scale (Observers's Assessment of Alertness/ Sedation scale) were assessed. RESULTS: The increasing concentrations of inhaled nitrous oxide resulted in significant reduction of the OAA/S scale but in no change of BIS. Concentrations of nitrous oxide exceeding 50% affected behavior or emotion of the patients. CONCLUSIONS: Following increasing concentrations of inhaled nitrous oxide, sedation score was reduced significantly but BIS was not affected.