The effects of anesthesia and surgical procedures on natural killer (NK) cell activity were studied. The data indicated that splenic lymphocytes taken from mice 1 to 5 days after surgery showed significantly diminished activity of natural killing. When splenic lymphocytes were treated by anti-Thy 1 antibody and complement, NK activity to Lewis lung carcinoma cells was remarkably depressed in normal mice, but was not depressed in laparotomized mice. Peripheral lymphocytes from cancer patients following major surgery also showed depressed NK activity. The suppression was first detected during the operation. In patients undergoing major gastrointestinal surgery, the suppression was at its maximum during first three days and decreased to control levels by the day 7 to 14. Following major thoracic surgery, the suppression continued more longer.