Expression levels of T-cell receptor (TcR)-associated zeta chain were reported to reflect functional competence of T lymphocytes in patients with cancer. This retrospective study was performed to evaluate zeta chain expression in circulating T cells obtained from clinical responders and nonresponders among 19 patients with advanced ovarian carcinoma treated with intraperitoneal interleukin-2 (IL-2) biotherapy. Banked lymphocytes, which were collected from the patients who participated in a phase I clinical trial performed between 1987 and 1990, were used for quantitative flow cytometry to measure zeta-chain expression in T lymphocytes prior to and at the end of therapy. The data were correlated with 7-year survival. The patients (9 responders and 10 nonresponders) were stratified into two groups based on zeta chain expression in CD3+ T cells above or below the mean. Patients with lower zeta expression in circulating T cells had shorter survival compared to patients whose T cells expressed high zeta. Pretherapy zeta expression was significantly lower (p = 0.03) in CD8+T cells of nonresponders than in CD8+T cells of normal controls. In patients with advanced ovarian carcinoma, low expression of the zeta chain in peripheral blood T cells prior to biotherapy might both reflect a large tumor burden and predict a poor of response to IL-2 bio-therapy.