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It has been reported that naloxone antagonizes general anesthesia in rats when the tail clamp is used as a painful stimulus to assess anesthesia.1 The authors' hypothesis is that this antagonism is to the analgesic component of anesthesia only, and that anesthesia assessed by a non-painful stimulus would not be antagonized by naloxone. Therefore, the anesthetic potency of nitrous oxide in mice was measured using loss of the righting reflex as a non-painful stimulus. Naloxone, 2 and 16 mg/kg, intrapcritoncally, failed to antagonize nitrous oxide anesthesia measured 14–39 min after injection. Thus, 19 min after injection of naloxone, 2 mg/kg, the nitrous oxide ED50 was 1.25 ± 0.060 atm (n = 35), compared with 1.19 ± 0.053 atm (n = 35) after injection of saline solution (control). Following naloxone, 16 mg/kg, the nitrous oxide ED50 was 1.18 ± 0.059 atm (n = 35), compared with 1.22 ± 0.059 atm (n = 35) for saline solution. At neither dose of naloxone was the ED50 different from the control ED50, a finding that supports the authors' hypothesis.