Renal‐cell carcinoma (RCC) is one of the human cancers which respond best to immunotherapy. To better characterize the mechanism of the immune response in RCC, we analyzed the T‐cell receptor (TCR) β‐chain repertoire in primary RCC, metastases and paired peripheral blood lymphocytes (PBL) from 9 patients. For 3 of these, we also analyzed T cells recovered from normal kidney, or from tumor‐involved lymph nodes as well as tumor‐infiltrating lymphocytes (TIL) expanded in vitro for adoptive immunotherapy. The initial semi‐quantitative RT‐PCR method for definition of the Vβ gene usage was not informative enough to distinguish intratumoral clonal T‐cell expansions. In contrast, the length pattern analysis of the complementary determining regions 3 (CDR3) allowed oligoclonal T‐cell populations to be detected in fresh TIL from the 9 patients with RCC. Furthermore, these oligoclonal TIL populations were not present in normal renal tissue, autologous PBL or tumor‐involved lymph nodes. Different clonal T‐cell expansions were identified in the primary tumor and in a pulmonary metastasis from the same patient. The detection of clonal T‐cell populations observed in RCC suggests an in situ expansion in response to potential tumor antigens. This report provides an overall and accurate description of the T‐cell repertoire in a significant number of samples from patients with RCC. © 1996 Wiley‐Liss, Inc.