Non-small-cell lung cancers (NSCLC) are often infiltrated by T lymphocytes. It is postulated that the presence of tumor-infiltrating lymphocytes (TIL) reflects a local host immune response against autologous tumors. To identify the nature of NSCLC TIL, we have characterized the molecular structure of the TCRbeta chain expressed by infiltrating T cells and paired PBL from 9 untreated patients (4 LLC, 3 ADC and 2 SCC). For this purpose, we have used a high-resolution PCR-based method that determines CDR3 size patterns in TCRVbeta sub-families in fresh tumors and their corresponding autologous PBL samples. Oligoclonality in T-cell populations was observed in 3 (Hor, Bla and Pub) out of 9 tumor biopsies analyzed. In contrast, the TCR repertoire of the 6 following patients as well as of all the autologous PBL was diverse, with virtually all Vbeta specificities expressed. Among the 3 tumors with dominant T-cell clonotypes, relative expansion of some T-cell sub-populations was observed. One patient (Hor) with significant TCRVbeta21 expansion in tumor compared with autologous PBL, showed over-expression of a particular TCRVbeta chain with unique Vbeta21-D-Jbeta2.7 junctional region not detected in autologous PBL. TCRVbeta21/Jbeta2.7 expansion was also observed in IL-2-stimulated TIL cell lines and was confirmed by sequencing analysis of the V-D-J junctional region. These results strengthen the view that local antigen-driven selection may occur, and support the hypothesis that anti-tumor immune response may take place in some NSCLC.