Opioids are known to affect the MAC of inhalational anesthetics. We have determined the interaction between fentanyl and desflurane, following a bolus injection of fentanyl at induction in 134 adult patients. Five groups of patients were studied. Four groups received desflurane or isoflurane in oxygen with either fentanyl 3 or 6 μg/kg and thiopental 2–5 mg/kg given as a bolus injection at the time of induction. An additional group received desflurane in oxygen alone. Groups were stratified by age. MAC determination, in response to the stimulus of skin incision, was made using the “up-down'' method and logistic regression. The MAC of desflurane in oxygen was 6.3% (5.3–7.6%, 95% confidence interval [CI]). Fentanyl 3 μg/kg produced a fentanyl plasma concentration of 0.78 ± 0.53 ng/ml at skin incision and resulted in a MAC for desflurane of 2.6% (2.0–3.2%, 95% CI)%. Fentanyl 6 μg/kg produced a fentanyl plasma concentration of 1.72 ± 0.76 ng/ml at skin incision and resulted in a MAC for desflurane of 2.1% (1.5–2.6%, 95% CI). To compare recovery times to eye-opening and response to commands, patients were grouped according to the plasma fentanyl concentrations at the time of awaking. Recovery was faster in patients who received desflurane than in those who received isoflurane. The authors conclude that the MAC of desflurane is significantly reduced 25 min following a single dose of 3 μg/kg of fentanyl and that increasing the fentanyl dose to 6 μg/kg produces little further decrease in MAC. Desflurane is also associated with faster recovery from anesthesia than is isoflurane.