Opioids are frequently associated with side effects such as nausea, vomiting, and pruritus. We hypothesized that a prophylactic, continuous small-dose naloxone infusion would reduce the incidence of opioid-induced side effects without affecting analgesia or opioid consumption. In this prospective, double-blind, randomized, controlled clinical trial, we studied 46 postoperative patients (M:F, 21:25), averaging 14 +/- 2.5 yr and 53 +/- 17 kg, at the start of morphine IV patient-controlled analgesia. Patients were randomized to either saline (control, n = 26) or naloxone 0.25 microg . kg(-1) . h(-1) (n = 20). We found that the incidence and severity of pruritus (77% versus 20%; P < 0.05) and nausea (70% versus 35%; P < 0.05) was significantly more frequent in the placebo group compared with the naloxone group. Morphine consumption (1.02 +/- 0.41 mg . kg(-1) . d(-1) versus 1.28 +/- 0.61 mg . kg(-1) . d(-1)), pain scores at rest (4 +/- 2 versus 3 +/- 2), and pain scores with coughing (6 +/- 2 versus 6 +/- 2) were not different. We conclude that, in children and adolescents, a small-dose naloxone infusion (0.25 microg . kg(-1) . h(-1)) can significantly reduce the incidence and severity of opioid-induced side effects without affecting opioid-induced analgesia. When initiating morphine IV patient-controlled analgesia for the treatment of moderate to severe pain, clinicians should strongly consider starting a concomitant small-dose naloxone infusion.