A randomized, double-blind, prospective study was performed to determine the effects of perioperative administration of morphine or methadone on postoperative analgesic requirements and pain scores in 35 children aged 3 to 7 years undergoing major surgery. After a standardized induction of anesthesia, methadone or morphine, 0.2 mg/kg, was blindly administered, and supplemental doses were titrated to achieve comfort in the recovery room. Pain was assessed during the next 36 hours with a combination of validated behavioral and self-report measures. Patients in the methadone group required fewer supplemental opioid analgesic drugs during the next 36 hours, and reported lower pain scores. No patient had prolonged emergence from anesthesia, and no patient required naloxone or postoperative ventilatory assistance. No major adverse events occurred. We conclude that perioperative intravenous administration of methadone is an effective, inexpensive, and technologically simple means for providing prolonged analgesia for children after surgery.