It has been reported that a small population of peripheral T lymphocytes are capable of expressing V(D)J recombinase and initiating secondary V(D)J rearrangements. To determine whether RAG-expression and secondary TCR gene recombination in peripheral T cells are an antigen-driven process in secondary lymphoid tissues, we examined naive CD4(+) T cells, activated/memory CD4(+) T cells, and germinal center T cells from human tonsils. Our results showed that low levels of RAG-1 and RAG-2 mRNA were present in all T cell subpopulations except CD3(+)/CD4(-) T cells. LM-PCR analyses for double-strand DNA breaks showed that all the T cell subsets expressing RAG genes contain double-strand signal break ends, indicating ongoing TCR gene recombination. Continued RAG gene expression, introducing and repairing of double-strand DNA breaks at the TCR loci in the periphery may have significant implications in the development of some T cell neoplasms.