ObjectiveTo investigate the effects of methadone on the minimum alveolar concentration of isoflurane (ISOMAC) in dogs. Study designProspective, randomized cross-over experimental study. AnimalsSix adult mongrel dogs, four males and two females, weighing 22.8 ± 6.6 kg. MethodsAnimals were anesthetized with isoflurane and mechanically ventilated on three separate days, at least 1 week apart. Core temperature was maintained between 37.5 and 38.5 °C during ISOMAC determinations. On each study day, ISOMAC was determined using electrical stimulation of the antebrachium (50 V, 50 Hz, 10 mseconds) at 2.5 and 5 hours after intravenous injection of physiological saline (control) or one of two doses of methadone (0.5 or 1.0 mg kg−1). ResultsMean (±SD) ISOMAC in the control treatment was 1.19 ± 0.15% and 1.18 ± 0.15% at 2.5 and 5 hours, respectively. The 1.0 mg kg−1 dose of methadone reduced ISOMAC by 48% (2.5 hours) and by 30% (5 hours), whereas the 0.5 mg kg−1 dose caused smaller reductions in ISOMAC (35% and 15% reductions at 2.5 and 5 hours, respectively). Both doses of methadone decreased heart rate (HR), but the 1.0 mg kg−1 dose was associated with greater negative chronotropic actions (HR 37% lower than control) and mild metabolic acidosis at 2.5 hours. Mean arterial pressure increased in the MET1.0 treatment (13% higher than control) at 2.5 hours. Conclusions and clinical relevanceMethadone reduces ISOMAC in a dose-related fashion and this effect is lessened over time. Although the isoflurane sparing effect of the 0.5 mg kg−1 dose of methadone was smaller in comparison to the 1.0 mg kg−1 dose, the lower dose is recommended for clinical use because it results in less evidence of cardiovascular impairment.