Flumazenil is a potent-specific benzodiazepine receptor antagonist that has been shown to reverse CNS depressant effects mediated by benzodiazepine agonists. These agonists are known to affect the interaction of gamma aminobutyric acid (GABA) with its receptor. Because the action of volatile anesthetic agenst may be mediated by GABA, the authors determined the MAC of isoflurane in 16 dogs before and after one of three doses of intravenous flumazenil (0.15, 0.3, and 0.45 mg/kg) or the drug vehicle. The flumazenil produced a reduction in MAC from 1.39 ± 0.15% (mean ± SD) to 1.23 ± 0.11% after 0.15 mg/kg (P < 0.05), from 1.50 ± 0.35% to 1.08 ± 0.20% after 0.3 mg/kg (P < 0.01), and from 1.45 ± 0.14% to 1.09 ± 0.08% after 0.45 mg/kg (P < 0.01). Administration of drug vehicle produced no change in MAC. This reduction in isoflurane requirement by flumazenil may be due to its benzodiazepine receptor agonist action or its analgesic effect.