BACKGROUND: Intravenous and epidural clonidine both produce intraoperative hemodynamic stability and analgesia. The study was designed to investigate the analgesic effect of epidural or intravenous clonidine as the sole analgesic agent during and after operation. METHODS: Thirty nine patients undergoing total abdominal hysterectomy under general anesthesia with propofol were studied. At induction, clonidine infusion was started at the dose of 5 microgram/kg in 10 ml during 15 min, followed by 1 microgram/kg/hr (5 ml/hr) either by the epidural (n=19) or the intravenous route (n=20). During the operation, increase in blood pressure and heart rate that did not response to propofol (0.5 mg/kg) was treated with fentanyl (1 microgram/kg). Clonidine and propofol were discontinued at the beginning of peritoneal closure. Postoperative analgesia was assessed by patient-controlled analgesia (PCA) requirements and the visual analogue scale at rest and cough 0, 1.5, 3, 6, 12, 18, 24, 36 and 48 after surgery. Sedation score and side effects were also recorded. The concentrations of plasma epinephrine, norepinephrine and glucose were measured before and after clonidine infusion. RESULTS: The total doses of propofol and fentanyl used intraoperatively were not different between the two groups. Epidural and intravenous clonidine maintained the intraoperative hemodynamic stability at the same extent. The concentrations of plasma epinephrine and norepinephrine in the two groups were not increased after the clonidine infusion. Compared with intravenous clonidine, epidural clonidine significantly prolonged the time to first PCA use and reduced the postoperative PCA requirements during the first 12 hours. CONCLUSIONS: Epidural or intravenous clonidine used as the sole analgesic agent provided the hemodynamic stability associated with surgical stimulation without major side effect. Epidural clonidine produces better postoperative analgesia than intravenous clonidine.