Surgical stress is known to induce immunosuppression of T cell functions, but the mechanism behind this phenomenon is unclear. The purpose of this study was to determine whether surgical stress affects the expression of signal-transducing zeta molecules in peripheral T cells. In the present study, the expression of signal-transducing zeta molecules was studied by flow-cytometric analysis of permeabilized cells in peripheral blood mononuclear cells from 28 patients before and after surgery. The results demonstrate that T cell receptor (TCR) zeta levels in the peripheral T cells were lower on the 2nd or 3rd postoperative days (POD) compared to the preoperative period and recovered on the 7th POD in patients who received major surgery. Surface CD3 epsilon levels were also decreased after surgery but did not recover on the 7th POD. Culturing of T cells from the preoperative period with autologous monocytes from the 2nd POD induced a decreased expression of their TCR zeta. The reduction was prevented by the addition of catalase, a selective scavenger of hydrogen peroxide, indicating that this phenomenon was mediated by hydrogen peroxide. These results suggest that the decreased expression of TCR zeta molecules in peripheral T cells was induced by surgical stress, and was mediated by hydrogen peroxide derived from monocytes.