The immune response is impaired in patients with malignancy, and radiation therapy (RT) can exacerbate the cancer induced-attenuation of immune response. In order to search for the fine mechanisms behind the RT-induced attenuation of cell-mediated immune response, we measured the number of lymphocytes in peripheral blood, its subsets, and lymphoblast transformation induced by phytohemagglutinin (PHA), purified protein derivatives (PPD), mitogenic monoclonal antibody anti-CD3, and mitogenic combination of anti-CD2 antibodies 9-1 and 9.6 before and after RT in 19 patients with squamous cell lung cancer. Radiation therapy significantly decreased the total numbers of lymphocytes, CD-3, CD-4, and CD8-positive lymphocytes in peripheral blood. However, RT did not change the percentages of lymphocytes and its subsets. Radiation therapy increased the percentage of interleukin 2 (IL-2) receptor-positive lymphocytes, and RT significantly decreased in vitro lymphoblast transformation by PHA, PPD, or monoclonal antibodies to T-cell surface antigens (anti-CD2 or anti-CD3). In vitro incubation with IL-2 did not increase lymphoblast transformation by anti-CD3 before RT but significantly increased after RT. In conclusion, we suggest that one of the fine mechanisms behind the RT-induced suppression of immune responsiveness of patients with lung cancer is a defect in IL-2 synthesis by lymphocytes.