Ultralow doses of naloxone (0.001-0.1 microg/kg) produce analgesia in animal models. However, no clinical study has evaluated the combination of ultralow dose naloxone and morphine using patient-controlled analgesia (PCA). This randomized, double blind controlled study sought to determine if the combination of ultralow dose naloxone and morphine in PCA solutions affects opioid requirements, analgesia, and side effects. Two-hundred and sixty-five patients (18-65 years old) undergoing operations were randomized to receive PCA morphine 1 mg/ml (n=129) or PCA morphine 1 mg/ml plus naloxone 0.6 microg/ml (n=136). We evaluated the numbers of supplemental rescue doses, the cumulative dose of each PCA solution, pain intensity, pain relief, and opioid side effects during the first 24 h after surgery. We found that opioid requirements did not differ significantly between groups. The morphine+naloxone group on average required 0.07 mg more morphine (95% CI -1.1 to 1.3) during the 24 h than the morphine group. Pain intensity levels were also similar in both groups. The morphine+naloxone group had 0.06 units lower (95% CI -0.5 to 0.4) pain intensity levels than the morphine group. The morphine+naloxone group had a lower incidence of nausea and pruritus than the morphine group (P=0.01 for both symptoms). However, the incidence of vomiting, time to tolerate fluids, sedation, and urinary retention were similar between groups (all P values >0.1). The combination of ultralow dose naloxone and morphine in PCA does not affect analgesia or opioid requirements, but it decreases the incidence of nausea and pruritus.