The continuous infusion of low doses of naloxone has been reported to decrease postoperative opioid requirements and opioid side effects. However, there is no study that evaluates the effectiveness of the combination of a low dose of naloxone and morphine using patient-controlled analgesia (PCA). This prospective, randomized double-blind controlled study sought to determine if the combination of a low dose of naloxone and morphine in a PCA solution decreases postoperative opioid requirements and pain intensity. One hundred sixty-six patients (18-65 years old) undergoing operations of less than 3 h duration with an American Society of Anesthesiologist physical status I or II were randomized to receive PCA morphine 1 mg/cc plus normal saline or PCA morphine 1 mg/cc plus naloxone 6 microg/cc. Initial PCA settings were 0.5 cc per demand with a lockout time of 10 min. The numbers of 2.5 cc supplemental rescue doses and the cumulative dose of each solution were recorded in the first 24 h after the surgical procedure. Pain intensity and opioid side effects were evaluated every 10 min in the post-anesthesia care unit and every 4 h afterwards. Patient satisfaction was assessed at the end of the 24 h of observation. The morphine+naloxone group had more treatment failures (P=0.0001), higher opioid requirements (P=0.0097), greater pain intensity (P=0.04), less pain relief (P=0.004), and less satisfaction (P=0.01) than the morphine group. The incidence of side effects was similar in both groups (P=0.3). Contrary to previous reports, adding low doses of naloxone to a morphine PCA solution increases opioid requirements and pain.