Adult T-cell leukemia (ATL) is a mature T-cell malignancy which is caused by human T lymphotropic virus type-I (HTLV-I). Most of the ATL cells are CD3+, CD4+, CD8-, and T-cell receptor (TCR) alpha beta+ and also express activated antigens such as HLA-DR and interleukin-2 receptor (IL2R) alpha chain (CD25). Diminished surface expression of the TCR alpha beta/CD3 complex is a specific feature of ATL cells. Since the gene transcript for each chain of this complex has been detected and surface expression of this complex is further decreased, accompanied by the induction of IL2R alpha chain, after stimulation with anti-CD3 monoclonal antibody (mAb), the TCR alpha beta/CD3 complex is considered to be down-modulated in vivo. We recently reported four ATL patients whose leukemic cells were CD4-, CD8- (double-negative; DN), TCR alpha beta+. These DN-ATL cells expressed S100 beta protein which was not detected in CD4+ ATL cells. Similar to CD4+ ATL cells, surface expression of the TCR alpha beta/CD3 complex on DN-ATL cells was decreased in vivo despite the lack of CD4 or CD8 as coreceptor. Therefore, the TCR alpha beta+ T-cell with or without CD4 is the sole target of HTLV-I induced leukemia and the down-modulation of the TCR alpha beta/CD3 complex is considered to play a key role in the development of ATL.