The aim of this study was to develop a nonlinear mixed-effects model for the increase in cerebral oximetry (rSO2) during the rapid introduction of desflurane, and to determine the effect of hypocapnia and N2O on the model. Twelve American Society of Anesthesiologist physical status class 1 and 2 subjects were allocated randomly into an Air and N2O group. After inducing anesthesia, desflurane was then increased abruptly from 4.0 to 12.0%. The PETCO2, PETDESF and rSO2 were recorded at 12 predetermined periods for the following 10 min. The maximum increase in rSO2 reached +24-25% during normocapnia. The increase in rSO2 could be fitted to a four parameter logistic equation as a function of the logarithm of PETDESF. Hypocapnia reduced the maximum response of rSO2, shifted the EC50 to the right, and increased the slope in the Air group. N2O shifted the EC50 to the right, and reduced the slope leaving the maximum rSO2 unchanged. The N2O-effects disappeared during hypocapnia. The cerebrovascular reactivity of rSO2 to CO2 is still preserved during the rapid introduction of desflurane. N2O slows the response of rSO2. Hypocapnia overwhelms all the effects of N2O.