An impaired immune response is frequently observed in cancer patients and tumor-bearing mice. T-cells from mice with an experimental colon carcinoma were recently shown to express T-cell receptors that completely lacked the signal-transducing molecule CD3 ζ. Here, we have investigated the expression of the signal-transducing molecule ζ on lymphocytes from 14 patients with colorectal carcinomas using flow cytometric analysis of permeabilized cells with a monoclonal antibody (TIA-2; IgG1) specific for the cytoplasmic domain of the ζ chain as well as with immunoprecipitation and analysis on diagonal gel electrophoresis. We demonstrate that T-cells isolated from the tumors of the patients express significantly less CD3 ζ than T-cells in the peripheral blood of the same patients and that the peripheral blood of the patients express decreased levels of ζ chains, as compared to the levels found in lymphocytes from healthy controls. This decreased expression was also observed on ζ chains associated with the low affinity Fc receptor for IgG found in tumor-infiltrating NK cells (FcγRIIIAα; CD16).