We have compared the effects of 50% nitrous oxide and propofol, each administered concurrently with sufentanil, on the amplitudes and latencies of the compound muscle action potential (CMAP) response to transcranial electrical stimulation. Using a crossover design, 12 patients undergoing spinal surgery were exposed to both 50% nitrous oxide and propofol, the latter in a bolus-infusion regimen. Six patients received nitrous oxide first and six received propofol first. CMAP were recorded from the tibialis anterior muscle in response to both single and paired transcranial electrical stimuli. With single pulse stimulation, median CMAP amplitude was significantly greater during administration of nitrous oxide than propofol (nitrous oxide 335 (10th-90th percentiles 35-849) microV; propofol 36 (0-251) microV) (P < 0.01). With paired stimulation, there was no significant difference in CMAP amplitude during the two regimens (nitrous oxide 1031 (296-1939) microV; propofol 655 (0-1867) microV). The results indicate that propofol caused more depression of transcranial electrical motor evoked responses than 50% nitrous oxide but that the difference was probably clinically unimportant when a paired stimulation paradigm was used.