The transformation of lymphocytes in response to phytohemagglutinin stimulation was investigated in 77 patients undergoind anesthesia with and without coincident surgical operation. A depression of lymphocyte transformation apparent immediately following major operations was related primarily to the extent of tissue trauma and not to the anesthetic agent or technique. No depression of lymphocyte transformation followed anesthesia for treatment of pain or for minor operations. The total leukocyte count increased following general anesthesia for prolonged, traumatic operations, primarily because of an influx of neutrophils into the circulation. The leukocyte count did not increase after comparable operations performed with regional anesthesia. Postoperative depression of lymphocyte transformation is primarily due to nonspecific stress, perhaps because of associated sympathetic and adrenocortical stimulation. The depressant effect of anesthesia alone is minimal.