Epidural anesthesia attenuates surgical stress responses, such as the immune reaction and the pituitary hormone response. In the present study, we investigated the leukocyte response to initial surgical stimulation during upper abdominal surgery. Twenty adult patients (American Society of Anesthesiologists physical status I∼II) undergoing elective upper abdominal surgery were randomly assigned to an epidural anesthesia group or a general anesthesia group. An epidural catheter for postoperative pain relief was inserted into all patients before induction. In the epidural anesthesia group, patients obtained preemptive analgesia from Th4 to Th12 with 2% mepivacaine, whereas general anesthesia was maintained with 2 L of oxygen, 4 L of nitrous oxide, and 1% to 3% isoflurane. Changes in the leukocyte count and leukocyte subset distribution were determined before induction (baseline), immediately after induction, 5 minutes after induction, 5 minutes after skin incision, and 5 minutes after peritoneal incision. The changes were significantly different between the groups throughout the observation period (p<0.0001). The general anesthesia group demonstrated an increase in the leukocyte count compared with the baseline data 5 minutes after skin incision and 5 minutes after peritoneal incision (p<0.01). Moreover, these counts were significantly higher in the general anesthesia group than in the epidural anesthesia group (p<0.05). The subset distributions were also significantly different between the groups throughout the observation period (p<0.0001). In the general anesthesia group, neutrophils decreased and lymphocytes increased significantly compared with baseline (p<0.05). Moreover, lymphocyte distribution was significantly higher in the general anesthesia group than in the epidural anesthesia group 5 minutes after peritoneal incision. Thus, anesthesia modifies the early response of leukocytes to surgical stress. The link between the early leukocyte response to surgery and postoperative outcome is the next subject of investigation.