BACKGROUND: The bispectral index (BIS) measures changes in the interfrequency coupling of the electroencephalogram (EEG). The purposes of this study were (1) to determine whether BIS correlates with responses to command during sedation and hypnosis induced by propofol or propofol and nitrous oxide, and (2) to compare BIS to targeted and measured concentrations of propofol in predicting participants' responses to commands. METHODS: Twenty volunteers (15 men and 5 women, aged 22-50 yr) were given propofol by computer-controlled infusion, and EEG was recorded for off-line analysis of BIS. Responses to randomly ordered verbal commands or voice plus touch were measured with two categorical scales (CS1 and CS2, respectively). All subjects received a propofol infusion targeted to achieve effect site concentrations of 1, 2, 4, 2, 1, and 0 microg/ml. Ten participants had repeated infusion, whereas 10 others breathed 30% nitrous oxide and oxygen and received a propofol infusion targeted for 0.5, 1, 2, 4, 2, 1, 0.5, and 0 microg/ml. Five minutes after each targeted concentration had been reached, CS1, CS2, and arterial propofol concentration were determined. The area under the receiver operating characteristic curve was used to compare the accuracy of (1) BIS, (2) targeted propofol concentration, (3) measured concentration, and (4) treatment history as predictors of response. RESULTS: Bispectral index was a strong predictor of CS1 and CS2 (P < 0.0001) and significantly more accurate than targeted or measured propofol concentrations (P < 0.0003 and P < 0.003, respectively). It also provided additional predictive power when combined with treatment history (P < 0.02). Nitrous oxide slightly decreased the probability of response at a given value of BIS (P < 0.05), but accuracy was unaffected. CONCLUSIONS: Bispectral index accurately predicts response to verbal commands during sedation and hypnosis with propofol or propofol plus nitrous oxide. Accuracy is maintained in situations likely to be encountered during clinical use: when propofol concentrations are increasing or decreasing and when repeated measurements are made over time.