Background: Intraoperative stress may evoke various changes in hormonal secretion and autonomic nervous system activity. We designed this study to investigate the effect of combined spinal-epidural anesthesia on stress hormone responses. Methods: Thirty women more than 60 years of age, undergoing bilateral total knee replacement surgery were studied. Patients were randomized to receive either general anesthesia (group I), or combined spinal-epidural anesthesia (group II). Blood samples were obtained immediately before anesthesia induction, immediately after skin incision, after first knee prosthesis insertion, and end of operation, immediately for measurement of cortisol, epinephrine, and norepinephrine. Results: The plasma concentration of cortisol, epinephrine and norepinephrine were significantly lower in group II after the prosthesis insertion and at the end of operation, immediately. The plasma concentration of cortisol was significantly higher than basal values in both of two groups through the surgery. Conclusions: Combined spinal-epidural anesthesia has the blocking effect of releasing catecholamine during total knee replacement surgery and immediately after the surgery. The effect of combined spinal-epidural anesthesia on stress responses during total knee replacement is better than that of general anesthesia. (Korean J Anesthesiol 2009;57:296∼301)