Active suppression by T regulatory cells plays an important role in the down-regulation of T cell responses to foreign and self-Ags. Thus far, the potential role of CD4+ CD25+ T cells in human tumors has not been reported. In this work we show that lung tumors contain large numbers of these cells and that they have constitutive high-level expression of CD152 (CTLA-4). Furthermore, the CD4+ CD25+ T cells mediate potent inhibition of autologous T cell proliferation. Finally, regulatory T cells from patient tumors failed to inhibit the proliferation of allogeneic T cells. Together these results suggest that the CD4+ CD25+ T cells found in lung tumors selectively inhibit the host immune response and therefore could contribute to the progression of lung cancer.