Background: It has been suggested that spectral entropy of the electroencephalogram as applied in the M-Entropy S/5 TM Module (GE Healthcare) does not detect the effects of nitrous oxide (N 2 O). The aim of this study was to investigate the effect on entropy by graded increases in N 2 O concentrations in the presence of a constant concentration of sevo urane, in the absence of surgical stimulation. Method: This single-blind, randomised study was conducted at an altitude of approximately 1 400 m. Patients received sevo urane 2% (1.7% at sea level) and N 2 O, at end-tidal concentrations of 0%, 10%, 20%, 30%, 40%, 50%, 60% or 70% (equivalent to 8.5%, 17%, 25.5%, 34%, 42.6%, 51.1% and 59.6% at sea level). Entropy was measured before, during and after N 2 O administration. The absolute changes and ratios o f entropy relative to the baseline were calculated. Between-and within-group comparisons were made using analysis of variance and covariance. Results: None of the entropy variables differed signi cantly within and between groups before and after N 2 O administration. Within-group analysis revealed that entropy during N 2 O administration was signi cantly lower than before or after N 2 O administration (P < 0.007). While a minor clinical but statistically signi cant linear relationship was observed between increasing N 2 O concentration and decreasing entropy from N 2 O 0% to 60%, a steeper and clinically important decrease (relative change > 20%) was noted at N 2 O > 60% (> 51% at sea level). Conclusions: The M-Entropy Module S/5TM responds to increasing concentrations of N 2 O in the presence of 2% (1.7% at sea level) sevo urane, in the absence of surgical stimulation. There is a linear relationship between increasing N 2 O concentrations and decreasing entropy with a steep and clinically important decrease at N 2 O > 60% (> 51% at sea level). The in uence of ambient pressure on the partial pressures, which determine the effects of anaesthetic agents, must be taken into account.