The effects of methadone and morphine maintenance on morphine self-administration were studied in the dog. Methadone was given passively for 2 weeks by continuous i.v. infusion. The amount of methadone administered daily was the same in mg/kg as the mean daily mg/kg of morphine the dogs had self-administered during the premaintenance control week. Morphine self-administration was markedly reduced initially but returned to normal levels within 2 weeks of methadone administration. Following the methadone maintenance period, morphine self-administration was increased over the premaintenance period for 2 weeks. A result similar to that with methadone was obtained in a second experiment when morphine was used as the maintenance drug in an amount that was three times the amount the dogs had been self-administering during the premaintenance control week.