BACKGROUND: We postulated that palonosetron, a novel antiemetic agent, might have the effect of alleviating injection pain from propofol and rocuronium. A double-blind, controlled study was undertaken to evaluate the effect of palonosetron on injection pain during total intravenous anesthesia and postoperative nausea and vomiting (PONV) using propofol-remifentanil in breast and thyroid cancer surgery. METHODS: Sixty patients were randomly allocated to one of two groups. Before injection of propofol and rocuronium, patients in group S (n = 30) received 4 ml of saline and patients in group P (n = 30) received 75 microg (1.5 ml) of palonosetron mixed with 2.5 ml of saline (n = 30). Patients were evaluated by a blinded anesthesiologist with regard to the scoring of injection pain of propofol, withdrawal response by rocuronium, PONV, shivering, postoperative pain, recall of pain, and overall satisfaction. RESULTS: The differences between groups in the incidence of injection pain due to propofol and rocuronium were insignificant. However, in group P, the severity of propofol-induced injection pain (3% vs. 33%, P = 0.003) and postoperative pain (P = 0.038) was significantly lower during the first 12 h after surgery. No differences were observed between the groups with respect to PONV, shivering, recall of pain, and overall satisfaction. CONCLUSIONS: We concluded that pretreatment of palonosetron was effective to reduce the severity of propofol-induced injection pain and early postoperative pain, although it did not reduce the incidence of injection pain from propofol and rocuronium.