The blood concentration associated with loss of response (LOR) to command in 50% of subjects (CP50(LOR)) is an important measure of anesthetic potency. We therefore determined the CP50(LOR) in 40 healthy surgical patients, aged 18-60 yr old, receiving propofol alone or propofol with 67% nitrous oxide (N2O). Patients were randomized to receive 100% oxygen or 67% N2O in oxygen via facemask. Three minutes later, a target-controlled propofol infusion was commenced at a concentration determined by the response of the previous patient in the same group. Fifteen minutes later, response to command was assessed by a blinded observer. Arterial blood samples were taken for propofol assay, and the bispectral index (BIS) was monitored continuously. At testing for response to command, both the measured and target propofol concentrations were significantly larger and BIS values significantly smaller in the propofol-alone group compared with the propofol-N2O group. The CP50(LOR) of propofol in the propofol-alone group was 4.58 mug/mL (95% confidence interval [CI], 1.14-15.36) and 2.67 microg/mL (95% CI, 2.28-3.17) in the propofol-N2O group. The BIS value when 50% of patients responded to command was 60 (95% CI, 55-65) in the propofol-alone group and 75 (95% CI, 73-83) in the propofol-N2O group.