We investigated, in a double-blind study, the effects of intraperitoneal local anesthetics during laparoscopic cholecystectomy. In Part A of the study 30 patients received 50 mL saline 0.9% (A 0), bupivacaine 0.125% (A 125), or bupivacaine 0.25% (A 25) intraperitoneally at the end of surgery. Mean maximum plasma concentrations of bupivacaine reached 0.48 mg/L (range 0.15-0.90 mg/L) in Group A 125 and 1.0 mg/L (0.35-2.10 mg/L) in Group A 25 within 15 min (range, 5-30 min). There was no significant difference in pain scores or opioid consumption (patient-controlled analgesia with piritramid): 24, 28, and 13 mg/24 h among the study groups, respectively (not significant). Postoperative respiratory function deteriorated in comparison to preoperative values in all study groups, but the forced vital capacity was significantly more impaired in Group A .25. In Part B, 24 patients received placebo (B 0) or bupivacaine 0.25% (B 25). Postoperative hypoxemic periods (oxygen saturation < 92%) were significantly more frequent in Group B 25. Considering the questionable benefits and the potential risks, we would not recommend the application of intraperitoneal bupivacaine during laparoscopic cholecystectomy.