This randomized double-blind placebo-controlled study was designed to evaluate the effects on postoperative pain of the local anesthetic, 0.5% bupivacaine with epinephrine, sprayed hepatodiaphragmatically under the surgeon's direct view during laparoscopic cholecystectomy. Metabolic endocrine responses to surgery (glucose and cortisol) and nonsteroidal anti-inflammatory drug requirements were investigated, as well as the presence of nausea, vomiting, and sweating. Local anesthetics or placebo solutions were given as follows. Immediately following the creation of a pneumoperitoneum, surgeons sprayed the first 20 mL of solution (S1), and an additional 20 mL of solution (S2) was sprayed at the end of the operation. Patients were classified into three groups (14 patients per group). Group A received 20 mL of saline during both S1 and S2, group B received 20 mL of saline during S1 and 20 mL of bupivacaine during S2, and group C received 20 mL of bupivacaine during both S1 and S2. The degree of postoperative pain was assessed using the visual analogue scale (VAS) and the verbal rating scale (VRS) on arrival in the recovery room and subsequently at time intervals of 4 h, 8 h, 12 h, and 24 h. The results of this study indicate a significant decrease of postoperative pain in patients treated with local anesthetic. VAS and VRS pain scores, as well as respiratory rate and analgesic requirements, were significantly lower in group C. The postoperative plasma cortisol level in group C was significantly lower than in groups A and B.