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A previous demonstration that the ratio of analgesic to anesthetic end-points is not constant across inhalation anesthetic agents implies that more than one mechanism of action may be operant in general anesthesia. We hypothesized that the endogenous opiate systems might account for this observed disparity in ratios. The tail flick ED50 (TFED50) in response to a heat stimulus, as an index of analgesia, and MAC as an index of anesthesia, were determined in rats treated with either saline or naloxone, 20 mg/kg, and exposed to halothane, enflurane, or isoflurane. Our findings confirmed those of Deady et al., showing a lack of uniformity of ratios of TFED50/MAC, with values of 0.90 ± 0.03 for halothane, 0.80 ± 0.04 for enflurane, and 0.70 ± 0.04 for isoflurane. Naloxone had no effect on TFED50, MAC, or their ratio. If the endogenous opiate system were involved in the analgesic effect of general anesthetics, naloxone would have affected the ratios. We conclude that opiate systems are not involved in the analgesic action of general anesthetics.