We investigated analgesia and the adverse effects of epidural sufentanil infusion in a double-blind randomized study of 37 patients undergoing thoracic surgery. Sufentanil 1 mu g/mL was administered at a thoracic (Ts, n = 12) or lumbar levels (Ls, n = 11), or combined with bupivacaine 1 mg/mL at a thoracic level (Tsb, n = 14). Postoperatively, the epidural infusion rate was titrated (4-20 mL/h) according to the visual analog pain scale when assessed during function (VAS-F) or the occurrence of side effects. When epidural analgesia failed, nonsteroidal antiinflammatory drugs (NSAIDs) were given. VAS-F was lowest in the Tsb group (Tsb < Ts = Ls) despite its having both the lowest rate of epidural infusion (Tsb < Ts = Ls). Sedation (Tsb < Ts < Ls) and hypercapnia (Tsb = Ts < Ls) occurred most frequently in the Ls group. Vital capacity (VC) was reduced in all groups by 43%-58% (Ls > Ts) and had recovered only partially at 24 h alter discontinuation of the epidural infusion. The slopes of the ventilatory response (minute ventilation [VE], inspiratory flow, and mouth occlusion pressure at 0.1 s [P-0.1]) to 7% CO2 decreased during treatment in Ls, Ts, and Tsb groups at the most by 73%, 55%, and 52% (not significant [NS] between groups), 59%, 45%, and 38% (NS between groups), and 81%, 43%, and 18% (Ls > Tsb), respectively. Twenty-four hours after discontinuation of the epidural infusion, there was a complete recovery of the VE, inspiratory flow, and P-0.1 response to CO2 in the Tsb group only. The study shows that, after thoracotomy, epidural sufentanil analgesia is optimal when tailored to the site of nociceptive input and combined with bupivacaine.