This study sought to better define the immunological impact of combining neoadjuvant total androgen suppression (TAS) with radiotherapy (xRT) in treating prostate cancer. Subjects selected (n=37) were stage I-II prostate cancer patients meeting the eligibility requirements for RTOG protocols 94-08 or 94-13. Flow cytometric monitoring of circulating T helper (T_h), T suppressor/cytotoxic (T_s), natural killer (NK) and B lymphocytes was performed weekly. Significant reduction of all lymphocyte subsets occurred as a result of xRT. Comparison between treatment groups demonstrated that the B lymphocyte and NK lymphocyte radioresponse was not influenced by TAS, but the T_h and T_s lymphocyte response was, with addition of TAS leading to less radiation-induced decline. The basis for this T cell response is unclear, but may involve a TAS-induced reduction of testosterone's immunomodulation of T cell proliferation and apoptosis and/or a direct, TAS-induced thymic stimulation. Our data suggest that addition of TAS to xRT appears to have no detrimental effects on lymphocyte subsets, and, indeed, may have favorable effects on T cells.