The effect of standard general (GA) and epidural anesthesia (EA) combined with GA on the response of surgical stress were compared. Thirty patients with ASA I-II physical status undergoing major abdominal surgery were randomly divided into two groups either to receive standard general anesthesia (Group-GA, n=15) or lombar epidural catheter placed to subjects in group GA-EA (n=15) before surgery. Following employment of 2% lidocaine 3 mL as test dose 0.25% bupivacaine 10 mL were given and then, general anesthesia was carried out. Heart rate, invasive blood pressure and central venous pressure were followed closely throughout the surgery. Mean arterial pressure and heart rate were recorded 6 times consecutively; before operation, at 30 min, 1 h, 2 hs, 6 hs and, 24 hours after skin incision. Serum levels of cortisol, glucose, interleukine-6 (IL-6), C-reactive protein, malonyldialdehyde, nitric oxide (NO) and superoxide dismutase were measured preoperatively and 2, 6, and 24 hours after the operation as parameters of stress response. Postoperative pain therapy was accomplished by PCA in group-GA and epidural PCA in group GA-EA. The degree of pain was evaluated according to VAS, at 1/2, 2nd, 6th, and 24th hours postoperatively. There was no difference between the two groups in terms of hemodynamic parameters (p>0.05). When compared to group-GA, VAS scores were lower in all periods in group GA-EA (p<0.05). IL-6 and NO levels increased in both groups but it was more pronounced in group-GA(p<0.05). There was no difference in the other stress parameters between the two groups. It was found that general anesthesia combined with epidural anesthesia was superior to general anesthesia for preventing stress response partly in patients undergoing major lower abdominal surgery.