Since laparoscopic cholecystectomy (LC) is widely recognised as being a "mild" or minimally invasive kind surgery, the aim of this prospective non-randomised study was to investigate the effect of intestinal manipulation on intestinal permeability and endotoxaemia in patients undergoing elective cholecystectomy, comparing the laparoscopic and laparotomic approaches. The intestine is susceptible to operations at remote locations, and the barrier function is altered during intestinal manipulation, leading to bacterial or endotoxin translocation into the systemic circulation. Fifty-three patients undergoing elective cholecystectomy were divided into two groups on the basis of laparotomic (n = 27) or laparoscopic (n = 26) approach. Intestinal permeability was measured preoperatively, and on day 1 and day 3 after surgery using the lactulose/mannitol absorption test. Serial venous samples were taken at 0, 30, 60, 90, 120 and 180 minutes, and at 12, 24 and 48 hours after surgery, for endotoxin measurement using the chromogenic limulus amoebocyte lysate assay. Intestinal permeability was significantly increased on day 1 [0.106 +/- 0.0005 (mean +/- S.E.M.)] in the laparotomic group compared to the preoperative level (0.019 +/- 0.005, p < 0.05) and to the laparoscopic group on day 1 (0.019 +/- 0.005, p < 0.05) which showed no change in comparison with the preoperative level. A significantly higher concentration of systemic endotoxin was detected intraoperatively in the laparotomic group of patients in comparison with the laparoscopic group (p < 0.05). There was significant positive correlation between systemic endotoxaemia and intestinal permeability (rs = 0.958; p = 0.001). An increase in intestinal permeability and degree of systemic endotoxaemia are observed during laparotomic cholecystectomy. This suggets that intestinal manipulation may impair the mucosal barrier function of the gut and contribute to the systemic inflammatory response seen in open cholecystectomy.