Background. Intravenous and epidural clonidine both produce postoperative analgesia. Several experimental reports demonstrate a spinal site of action for the analgesic effects of this alpha2-adrenoceptor agonist. Therefore, the authors evaluated the clinical analgesic benefits of using clonidine, both intra- and postoperatively, by the epidural or the intravenous route. Methods: Using a randomized prospective double-blind study design, 40 patients, between 18 and 50 yr of age, undergoing intestinal surgery under general propofol/nitrous oxide anesthesia, were enrolled. Before anesthesia, an epidural catheter was inserted at the L1-L2 interspace. At induction, a clonidine infusion was started at the doses of 4 mug/kg in 1 0 ml during 20 min, followed by 2 mug . kg-1 . h-1 (5 ml/h) during 12 h, either by the epidural (group 1) or by the intravenous (group 2) route. Intraoperatively, increased blood pressure and heart rate not responding to additional propofol bolus (0.5 mg/kg) was treated with a bolus of alfentanil (7 mug/kg). Postoperatively, morphine boluses (1.5 mg) were given through a PCA device according to the patient's need. Intraoperative analgesia was assessed by the alfentanil requirements. Postoperative analgesia was assessed by recording the morphine requirements, the visual analogue scale (VAS) at rest and after mobilization, and the patients' analgesia scale at 0, 3, 6, 12, 18, 24, and 36 postoperative hours. Sedation analogue scale and side effects were also recorded. Heart rate and blood pressure were particularly detailed during the first 2 h of the clonidine infusion. Plasma clonidine concentrations were measured after 20 min and 6, 12, and 24 h. Results: Epidural clonidine significantly reduced the intraoperative alfentanil requirements (0.93 +/- 1.2 in group 1 vs. 2.4 +/- 1.8 mg in group 2). The postoperative morphine requirements were also reduced during the first 6 h (8.3 +/- 5.8 in group 1 vs. 17.8 +/- 13.4 mg in group 2). The VAS were comparable in both groups, despite the better patients' analgesia score reported in the epidural group during the first 12 h. There was no difference in sedation score at any time interval considered. Epidural and intravenous clonidine reduced heart rate and blood pressure to the same extent. The plasma clonidine concentrations were less in the epidural group only after the loading doses. Conclusions: Epidural clonidine reduces the intra- and early postoperative analgesic requirements when compared with the same dose given by the intravenous route. The side effects were similar with the two routes of administration