Serial changes of immunosuppressive activity of serum and cell-free skin bleb fluid that can suppress the activity of acid a-naphthyl acetate esterase (ANAE) of lymphocytes and phagocytosis of macrophages were detected by immunoregulatory tests in vitro in 50 lung cancer and 42 esophageal cancer patients. In comparing these tests with those of 53 cases of noncancerous thoracic lesion and 69 normal adults, the immunosuppressive activity of serum and skin bleb fluid from cancer patients is significantly higher than that of noncancerous thoracic lesions and normal individuals (P less than .01). The activity is related to the stages of cancer, the size of primary tumor, the presence of lymph node metastasis, and tumor resect-ability, but not to histological classification, sex, and age. The immunosuppressive activity of serum and skin bleb fluid decreased gradually after the removal of the tumor and was eliminated on the 30th postoperative day. These results suggest that serum and skin bleb fluid from cancer patients may contain immunosuppressive factors that can suppress the immune responsive functions of lymphocytes and macrophages in vitro in a manner similar to that seen in vivo. Therefore, complete surgical removal of cancer is likely the most effective immunotherapy.