BackgroundFentanyl produces a minimal reduction in the minimum alveolar concentration of sevoflurane to prevent response to a verbal command in 50% of patients (MACawake) at low but analgesic plasma concentrations. The reduction in MACawake, however, is still unknown at higher fentanyl concentrations. The reduction in the MAC of sevoflurane by fentanyl has not been described accurately. The purpose of this study was to determine the MACawakeand MAC reduction of sevoflurane by fentanyl.MethodsNinety‐two patients were randomly allocated to seven fentanyl concentration groups (target plasma concentrations of 0, 1, 1.5, 3, 6, 10, and 14 ng/ml). Responses to verbal command were observed for MACawakeassessment at predetermined sevoflurane concentrations. Thereafter, in patients whose target fentanyl concentration was 0 to 10 ng/ml, responses to skin incision were observed for MAC assessment at new steady‐state sevoflurane concentrations. The reduction in the MACawakeand MAC of sevoflurane by the measured fentanyl concentration was calculated.ResultsThere was an initial steep reduction in the MAC of sevoflurane by fentanyl, with 3 ng/ml resulting in a 59% MAC reduction. A ceiling effect was observed, with 10 ng/ml providing only a further 17% reduction in MAC. The initial reduction in MACawakewas not as steep as that in MAC. Fentanyl reduced MACawakeby approximately 24% at a plasma concentration of 3 ng/ml. Although the reduction curve of MACawakewas parabolic, no manifest ceiling effect was observed at concentrations administered in the present study.ConclusionsThe reduction in sevoflurane requirements for loss of consciousness and skin incision by fentanyl was determined. Fentanyl reduced both requirements, but the mode of the reduction was not comparable.