Background: Several studies have suggested that the spinal cord may be an important site of anesthetic action and have established that general anesthetics potentiate the effects of GABA at the GABAA receptor. It was, therefore, hypothesized that the suppression of nocifensive movements during anesthesia is due to an enhancement of GABAA receptor-mediated transmission. Therefore, the aim of this study was to determine behaviorally whether intrathecal GABA, glycine, or opioid receptor antagonists may change the anesthetic effect of isoflurane and enflurane. Methods: The minimal alveolar concentration (MAC) of isoflurane and enflurane was determined in Sprague-Dawley rats, by the tail-clamp technique. First, MAC was determined and then concentration of each inhalation agent was increased by 0.2% from the sub-MAC level. Moving latencies were observed after the intrathecal administration of each receptor antagonist. Rectal temperature was measured and maintained at a steady level during the experiment. Results: The spinal antinociceptive effects of isoflurane and enflurane were significantly reversed by the GABAA receptor antagonist bicuculline and picrotoxin (P < 0.05). The rectal temperature was well maintained within the range of 37-39 degrees C. Conclusions: Our results suggest that the general anesthesia induced by isoflurane and enflurane, which are similar in terms of their action mechanism, is likely to be related to the spinal GABAA receptor system.