Renal cell carcinoma (RCC) is one human tumor to which the immune response may control the growth of tumor cells. These tumors are infiltrated by a large mononuclear infiltrate mainly composed of T lymphocytes. To characterize the lymphocytes infiltrating RCC, we analyzed the molecular structure of the T cell receptor (TCR) alpha and beta chains in tumor and paired peripheral blood lymphocytes from a series of 6 untreated patients. We first determined V alpha and V beta gene segment usage by PCR using a panel of V specific oligonucleotide primers (V alpha 1-w29 and V beta 1-w24). A highly diverse usage of TCR V alpha and V beta gene usage was observed in 5 of 6 tumors. In addition, the few tumor overexpressed V beta specificities detected by reverse transcription-PCR were shown to contain minor T cell expansions. Strikingly, 1 of the 6 tumor studied displayed a skewed TCR repertoire with V beta 4 transcript representing 25% of the TCR signals. Clonality of the tumor overexpressed V beta transcripts was analyzed by CDR3 size distribution analysis. In the particular tumor displaying a biased repertoire large expansions of T cell subpopulations were detected (particularly in V beta 4) specifically at the tumor site. Such T cells may be expanded locally in response to tumor antigens.