Loss of the T-cell receptor-associated zeta chain in tumor-infiltrating lymphocytes (TILs) has been proposed as one mechanism of acquired immunosuppression in cancer patients. Recent reports suggest that zeta-chain loss may be related to contaminating monocyte/macrophage protease activity. Using flow cytometry and Western blot analysis, we have confirmed the expression of zeta chain in matched peripheral blood mononuclear cells and TILs from eight patients with primary renal cell carcinoma, when the cells were exposed to sufficient quantity of protease inhibitors. A small decrease in zeta-chain expression was found in three TIL samples. The loss of zeta-chain expression that was noted by others may be related to differences in laboratory method, and the small changes we have noted are unlikely to be sufficient in explaining the immunosuppression of TILs.