The hypothalamic-pituitary-adrenal axis is an essential component for the maintenance of homeostasis following trauma. Major surgical trauma often induces overwhelming inflammatory responses leading to sepsis and organ dysfunction. This study was designed to evaluate the adrenal responses both before and after various degrees of surgical trauma and to determine the incidence of postoperative relative adrenal insufficiency resulting in the marked inflammatory response often associated with postoperative complications. Fifty-one surgical patients were divided into groups who underwent major, moderate, and minor surgeries. Before the operation and during resting conditions, a short corticotropin (ACTH) stimulation test was performed in each patient. The postoperative concentrations of serum cortisol, interleukin (IL)-6, IL-10, C-reactive protein (CRP), and plasma ACTH were measured. Fifty of 51 patients were identified as responders to ACTH. The postoperative cortisol levels were the same as those obtained by ACTH stimulation in highly and moderately stressful surgeries. The increases in postoperative IL-6 and CRP levels were greatest with major surgery, intermediate with moderate surgery, and least with minor surgery. Furthermore, plasma ACTH levels increased after major and moderate surgeries; however, there was no significant differences in postoperative serum IL-10 levels. Systemic inflammatory response syndrome (SIRS) was found in 11 of 17 patients (64.7%) who underwent major surgery and in 4 of 16 patients (25%) who underwent moderate surgery (p=0.037). The duration of SIRS was significantly longer in patients undergoing major surgery (62+/-20 hrs) than in patients undergoing moderate surgery (21+/-3 hrs, p=0.038). Postoperative complications were more frequent in patients undergoing major surgery (41.2%) than in patients undergoing moderate surgery (6.3%, p=0.039). Furthermore, there were significant differences in the length of the postoperative stay among the three groups (p<0.01). One nonresponder had serious postoperative inflammatory complications. These results suggest that a short ACTH stimulation test performed preoperatively is a helpful method for determining the maximal cortisol response to surgical trauma and to identify high-risk individuals and that a relative postoperative adrenal insufficiency may be closely related to the decreased cortisol secretion following major surgical trauma.