Thirty-six patients undergoing curative resection for colorectal cancer were studied to determine the effect of the tumor on lymphocytes circulating through it. In the venous blood draining the tumor, there was an increased percentage of natural killer (NK) cells (p = 0.001), no difference in overall NK cell function, and decreased T-lymphocyte activation (p = 0.035) and proliferation (p = 0.002) compared with the lymphocytes in the arterial blood supplying the tumor. There were no significant differences in the control group of 16 patients. Local effects of colorectal cancer may include the ability to down-regulate T and NK cell function while increasing the number of NK cells. Means of enhancing antitumor activity therapeutically in an adjuvant setting, possibly through the portal vein during surgery, need to be considered, especially in the light of the immunosuppressive effects of surgery.