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The neuromuscular effects of desflurane administered alone were studied in ten healthy human volunteers aged 20–27 yr. Also, the dose-response relationships of pancuronium and succinylcholine in surgical patients during anesthesia with desflurane (n = 13) were compared to those during isoflurane anesthesia (n = 14). In the volunteers, we measured the mechanical response of the adductor pollicis muscle to stimulation of the ulnar nerve in a train-of-four (TOF) sequence at 2 Hz and at tetanic frequencies of 50, 100, and 200 Hz, each administered for 5 s. Amplitudes of the first response (T1) in each TOF sequence and the ratios of the fourth TOF response (T4) to the first were similar at 3,6, and 9% desflurane and decreased significantly only at 12% (P < 0.05). Desflurane concentrations of 3–12% caused tetanic fade (>10% decrement in amplitude) at 50, 100, and 200 Hz. The addition of N2O and the duration of anesthetic exposure did not alter desflurane's neuromuscular effects. The only neuromuscular variable influenced by CO2 was T1 amplitude, which decreased as arterial CO2 tension (PaCO2) increased. The doses of pancuronium that depressed T1 amplitude by 50% (ED50) were similar during anesthesia with 1.25 MAC desflurane, 10.5 ± 2.8 μg/kg (mean ± SD) and 1.25 MAC isoflurane, 12.3 ± 5.0 μg/kg. The ED50doses of succinylcholine were similar during anesthesia with desflurane 132 ± 76 μg/kg and isoflurane 123 ± 36 μg/kg. We conclude that desflurane significantly depresses neuromuscular function and augments the action of pancuronium and succinylcholine to a degree similar to that of isoflurane.