It has been postulated that cortisol and interleukin-6 play a significant role in the modulation of the early inflammatory response following surgical intervention. There are no available data on the normal responses of these mediators following major laparoscopic procedures. The purpose of this study was to assess changes in cortisol (by fluorescence polarization immunoassay), interleukin-6 (by enzyme-linked immunoassay), and interleukin-1 (by enzyme-linked immunoassay) after elective laparoscopic colon resections. All patients undergoing colon resection between February 1, 1992 and April 30, 1992 were eligible for study. Selection of laparoscopic (N = 12) vs. open (N = 41) resection was determined by the attending surgeon. All patients received a standard general anesthetic with endotracheal intubation. Cortisol, interleukin-6, and interleukin-1 were measured at preinduction, 1 hour, 2 hours, 3 hours, 4 hours, and 5 hours after the induction. Interleukin-6 and interleukin-1 were additionally measured at 12 hours, 24 hours, and 72 hours after induction. Comparisons were made between the laparoscopic patients (N = 12) and age, sex, and operation-matched open patients (N = 12). Cortisol levels rose in the early postoperative period in both open and laparoscopic groups with no significant differences occurring between the cohorts at any of the measured time intervals. The interleukin-6 levels of the laparoscopic cohort (N = 12) were significantly lower than those of the open cohort (N = 12) between 3 and 24 hours postinduction (P < 0.05). Interleukin-1 levels remained undetectable in virtually all patients irrespective of operative technique or postoperative interval. There was no correlation between peak interleukin-6 levels and operative times (laparoscopic, r = 0.31; open, r = 0.36) or blood loss (laparoscopic, r = 0.10; open, r = 0.20). The results indicate that laparoscopic colon resections do not appear to alter cortisol or interleukin-1 responses when compared with open colon resection. There is, however, a significant blunting of the interleukin-6 response associated with the use of laparoscopic techniques for colectomy compared with standard laparotomy.