Several previous studies concluded that opioid receptors do not mediate the capacity of inhaled anesthetics to produce immobility in the face of noxious stimulation because administration of naloxone (a nonspecific opioid receptor antagonist) does not increase the minimum alveolar anesthetic concentration (MAC) of inhaled anesthetic that produces immobility in 50% of subjects given a noxious stimulation. In contrast, a recent study found that 0.1 mg/kg naloxone given intraperitoneally increased sevoflurane MAC in mice by 18% (P < 0.01). We repeated the recent study with sevoflurane in the same strain of mice, administering nothing (control), 0.1 mg/kg, and 1.0 mg/kg of naloxone. Our study differed in that we also tested a parallel group given saline rather than naloxone. We were blinded to drug administration. MAC decreased 4.8% ± 11.0% (mean± sd) and 2.4% ± 12.5% with the first and second administrations of saline. Similarly, MAC decreased 4.7% ± 7.1% and 5.5% ± 10.0% with the administration of 0.1 mg/kg and 1.0 mg/kg of naloxone. We do not find that naloxone increases MAC. Opioid receptors do not underlie a portion of the capacity of inhaled anesthetics to produce immobility.