Although epidural anesthesia prevents immune suppression during surgery, no reports have elucidated how epidural block affects immune response in nonsurgical patients. We examined changes in proportion of lymphocyte subsets and in natural-killer (NK) cell activity in patients with and without pain. Fifteen patients with pain (Pain group) and 15 preoperative patients without pain (Preoperative group) received three different treatments in random order: epidural block with 7 mL 1% lidocaine, epidural injection of an identical volume of normal saline, and IV injection of 1 mg/kg lidocaine. Blood samples were drawn before and after 30, 60, and 120 min of treatment. During epidural block at 30 and 60 min, both groups showed significantly decreased epinephrine, norepinephrine, and cortisol levels, and the proportion of NK cells decreased, whereas the CD4+/CD8+ ratio increased significantly. NK cell activity in both groups decreased significantly at 30 and 60 min. At 120 min, the variables had all returned to preblock values. During treatments with saline and IV lidocaine, neither group showed significant changes in any of the above variables. We conclude that epidural block causes a transient and significant alteration of lymphocyte subsets and NK cell activity regardless of pain status.