We and others have shown decreased expression of T‐cell receptor‐CD3‐associated signal transducing ζ molecules (TCRζ) in tumor infiltrating and peripheral T cells of patients with advanced cancer. In the present study, we performed adoptive immunotherapy (AIT) with tumor‐associated lymphocytes (TAL) in patients with gastric (n = 11) and colon (n = 3) cancer with stage IV and investigated whether the alteration of signal transducing molecules was observed with AIT, compared to an untreated control group (n = 13). Autologous TALs isolated from malignant ascites or pleural effusion were cultured with stimulation of autologous tumor in the presence of interleukin‐2 (IL‐2) and were transferred to the patients. TCR ζ expression in peripheral T cells was measured by flow cytometric analysis of permeabilized cells with anti‐ζ monoclonal antibody (MAb) (TIA‐2) before and after AIT. We confirmed the down‐regulation of TCR ζ expression in peripheral blood lymphocytes (PBL) of patients with gastric and colon cancer with stage IV compared to healthy donors (n = 15). AIT induced up‐regulation of TCR ζ expression in 2 of 14 treated patients, caused no significant change of TCR ζ expression in 7 patients and induced further down‐regulation in 5 patients. The patients who achieved clinical responses (n = 3) with AIT showed no significant change of TCR ζ expression. On the other hand, in the control group without adoptive transfer, further down‐regulation of TCR ζ expression was observed during the corresponding periods, paralleling disease progression. Taken together, TCR ζ expression in the patients was further down‐regulated, corresponding to disease progression in individual cancer patients. In some patients, AIT could induce increased or stable TCR ζ expression. The quantitative analysis of TCR ζ expression might provide vital information that can be used to optimize therapy by preserving immune functions within cancer patients. Int. J. Cancer 78:301–305, 1998.© 1998 Wiley‐Liss, Inc.