BACKGROUND: Adenosine has been shown to have a wide spectrum of unique pain-relieving effects in various clinical situations. The aim of this study was to investigate the effects of intraoperative adenosine infusion on acute opioid tolerance and opioid induced hyperalgesia induced by remifentanil in adult patients undergoing tonsillectomy. METHODS: For this study, ninety patients were randomly allocated into groups that receive either adenosine (adenosine group) or saline (remifentnail group) intravenously under remifentanil based anesthesia and saline (sevoflurane group) under sevoflurane anesthesia. The patients in adenosine group received adenosine at dose of 80 microg/kg/min, and those in remifentnail group and sevoflurane group received an equal volume of saline 10 minutes after the induction of anesthesia until the end of surgery. Intraoperative evaluation included time weighted mean remifentanil dose, and postoperative evaluations included degree of pain severity at 1, 6, 12, and 24 hours, time to first postoperative requirement, and analgesic dose required during 24 hours after operation. RESULTS: Time weighted mean remifentanil dose during intraoperative period in adenosine group was significantly lower than that of remifentnail group (P = 0.00). The first postoperative analgesic were required earlier in remifentanil group than sevoflurane group or adenosine group (P = 0.00). Pethidine requirement during 24 hours in sevoflurane group and adenosine group was significantly lower than that of remifentnail group (P = 0.00). The visual analog scale scores for pain in sevoflurane group and adenosine group were significantly lower than those of remifentnail group for 12 hours after operation (P = 0.00). Incidence of hypotension (P = 0.024) and number of ephedrine administered (P = 0.011) in adenosine group were significantly higher than those of sevoflurane group. CONCLUSIONS: The above results suggest that intraoperative adenosine infusion prevent acute opioid tolerance and opioid induced hyperalgesia induced by remifentanil.