BACKGROUND: Ondansetron is effective for the treatment of intrathecal morphine-induced pruritus. There is evidence that kappa-opioid receptor agonists have antipruritic activity. Pentazocine is an agonist of kappa-opioid receptors and partial agonist at mu-opioid receptors. We therefore performed a randomized, double-blind trial to compare the efficacy of pentazocine and ondansetron for the treatment of pruritus associated with intrathecal injection of morphine in patients undergoing cesarean delivery. METHODS: Two hundred eight parturients who developed moderate to severe pruritus after the administration of intrathecal morphine were randomly allocated to 2 groups: IV pentazocine 15 mg (n = 104) and IV ondansetron 4 mg (n = 104). The successful treatment of pruritus (no or mild pruritus) and other adverse effects were determined 15 min after study drug administration, and patients were observed for recurrence of pruritus for 4 h. RESULTS: The treatment success rate at 15 min was higher in the pentazocine group (96.1%) than in the ondansetron group (80.8%) (95% confidence interval of difference: 7.0%, 23.8%; P = 0.001). The recurrence rate of moderate to severe pruritus within 4 h after treatment in the pentazocine group (12.0%) was lower than in the ondansetron group (32.1%) (P = 0.001). There were no significant differences between groups in nausea/vomiting, sedation, shivering, pain scores, and pain at injection site. No respiratory depression was observed. CONCLUSIONS: Pentazocine 15 mg is superior to ondansetron 4 mg for the treatment of intrathecal morphine-induced pruritus and has a lower recurrence rate. The side effects after treatment are mild.