The efficacy of interpleural administration of sufentanil, 50 μg, was compared with that of 150 mg of bupivacaine, 0.5%, with epinephrine, 5 μg/mL, or saline, in 30 patients (N = 10 in each group) undergoing lateral thoracotomy. Sufentanil, bupivacaine, or saline was administered interpleurally after induction of anesthesia with sufentanil, 1 μg/kg intravenously, and thiopental, 2 to 5 mg/kg. Anesthesia was maintained with nitrous oxide, 66%, and halothane, 0.3% inspired concentration. Supplementary intravenous sufentanil, 25 μg, was given whenever the systolic arterial blood pressure increased more than 15 mmHg above the preoperative value, heart rate exceeded 90 beats/min in the absence of hypovolemia, or when other autonomic or somatic signs of inadequate anesthesia occurred. The additional intravenous sufentanil requirement and the incidence of hypotension were compared between the groups. All patients in the placebo group needed supplementary sufentanil. Significantly fewer patients in the interpleural sufentanil (N = 1, P < 0.0002) and bupivacaine (N = 1, P < 0.0002) groups required supplementary sufentanil compared to the placebo group (N = 10). The time from interpleural administration of the study drug to the first administration of postoperative analgesic was significantly longer ( P < 0.001) in the sufentanil group (228 ± 72 min) and bupivacaine group (242 ± 76 min) compared to the placebo group (141 ± 50 min). It was concluded that interpleural administration of either sufentanil or bupivacaine contributes to intraoperative analgesia during thoracotomy.