The immunosuppression caused by surgical stress in cancer therapy may affect the prognosis of patients by enhancing the residual tumors. An investigation of changes of lymphocyte subsets and suppressor cell activity during the postoperative course was performed for the analysis of the immunosuppression caused by the surgical stress in patients with gastrointestinal cancer. In patients undergoing the surgical stress of total gastrectomy or esophageal resection, CD4+2H4- (helper T) and CD8+CD11-(cytotoxic T) cells significantly depressed on day 1 after operation and remained until day 7. In these patients, CD4+2H4+ (suppressor inducer T) cells significantly increased from just after the operation, remained to increase until day 1 after operation and recovered to the preoperative level thereafter. Concanavalin A-induced suppressor cell activity peaked on day 4 and decreased thereafter. However, in patients with benign disease, decreases of helper and cytotoxic T cells were found to a slight degree. The population of lymphocytes with surface receptors for a soluble suppressor factor significantly increased on day 1 after operation in patients receiving esophageal resection and continued to increase until day 30. In patients with preoperative treatment of PSK and cyclophosphamide, the decreases in helper and cytotoxic T cells and the increase in suppressor inducer T cells were significantly blocked during the postoperative course. Thus, these results indicate that extensive surgical stress such as total gastrectomy and esophageal resection may be attributable to the immunosuppression produced by the induction of suppressor cells, and the necessity of pre- and post- operative immunotherapies may be indicated for a better prognosis.