© The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: email@example.com. BACKGROUND: Intrathecal morphine-induced pruritus is a very common side-effect that is difficult to prevent or treat. Central and peripheral mechanisms are believed to be involved. The aim of this study was to determine if a peripherally acting, μ-opioid antagonist would reduce morphine-induced pruritus. METHODS: We conducted a multicentre, randomized, blinded, placebo-controlled trial of women having elective Caesarean section under spinal anaesthesia with intrathecal morphine 100 μg. After delivery, participants received either subcutaneous methylnatrexone bromide 12 mg (MNTX group, n=69) or saline (placebo group, n=68). Pruritus, nausea, pain, analgesic use, and side-effects were assessed at 2, 4, 8, and 24 h. The primary outcome was the severity of pruritus (0-10 score). RESULTS: One hundred and thirty-seven women completed the study, with five major protocol violations. There was no statistically significant difference between the MNTX and placebo groups for the median (IQR) pruritus AUC scores [24 (9-47) vs 36 (11-68), median difference 8.5, 95% confidence interval (CI) 0-20, P=0.09] or the worst pruritus score [3 (2-7) vs 5 (2-6), median difference 1, 95% CI 0-2, P=0.24]. The incidence of pruritus was 84% in the MNTX group and 88% in the placebo group (P=0.48). Analgesic and gastrointestinal outcomes did not significantly differ between the groups. CONCLUSIONS: A single dose of subcutaneous methylnaltrexone bromide 12 mg did not reduce the overall severity or incidence of pruritus. In this study, treatment with a peripherally acting μ-opioid antagonist was generally ineffective against intrathecal morphine-induced pruritus, but a small clinical effect cannot be excluded. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12611000345987).