Both inflammatory and anti-inflammatory mediators are released into the circulation during major abdominal surgery. In addition, some of these mediators have been detected postoperatively in peritoneal fluids. Thus, it appears that the peritoneum may be a potential source of circulating immunomodulators following major abdominal surgery. With this in mind, we quantified the intraoperative production of interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1) by human peritoneum. A small chamber was sewed to the parietal peritoneum of 19 patients at the beginning of the operation. This chamber was perfused with buffered salt solution, and the perfusate was collected hourly and assayed for IL-6 and MCP-1 concentrations by enzyme-linked immunosorbent assay. Expression of the corresponding mRNAs was determined by reverse-transcription polymerase chain reaction from additional peritoneal biopsies taken at the beginning and at the end of operation. Peritoneal production of IL-6 and MCP-1 started within the first hour of operation and continued with increasing amounts of up to 435 (43-1925) pg/cm2/h [median (range)] of IL-6 and 435 (59-1930) pg/cm2/h of MCP-1. There was induction of peritoneal IL-6 and MCP-1 mRNA expression. A suppressed MCP-1 production was seen only in one patient who suffered from severe septic complications in the postoperative course. Using a new technique that allows for the quantification of local cytokine production in vivo, we demonstrated that the peritoneum rapidly reacts to abdominal surgery with increased production of IL-6 and MCP-1. Early detection of impaired production may help to identify patients at risk of postoperative septic complications.