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The minimum alveolar anesthetic concentration (MAC) of desflurane (I-653) was determined when administered with 60% nitrous oxide (N2O) in oxygen after a standardized induction sequence consisting of 0, 3, 6, or 9μg/kg intravenous (IV) fentanyl followed by 3–6 mg/kg IV thiopental and 1.5 mg/kg IV succinylcholine. For comparison, we also determined the isoflurane MAC with 60% N2O in oxygen after an induction dose of 3μg/kg IV fentanyl and similar doses of thiopental and succinylcholine. All patients were undergoing elective surgical procedures. The minimum alveolar anesthetic concentration in patients given isoflurane and 60% N2O with 3 μg/kg fentanyl was 0.4%, approximately 20% below previously reported MAC values for isoflurane with 60% N2O alone. The minimum alveolar anesthetic concentration of desflurane with 60% N2O plus 0, 3, 6, and 9μg/kg IV fentanyl was 3.7%, 3.0%, 1.2%, and 0.1%, respectively. Thus, the MAC-lowering effect of 3μg/kg IV fentanyl appears to be similar with both isoflurane and desflurane. Fentanyl, 3–9μg/kg IV, produces dose-dependent decreases in the MAC of desflurane.