We studied 18 patients with myelodysplastic syndrome (MDS), measuring clonality and T-cell receptor Vbeta (TCRBV) expression of CD4 and CD8 T cells by polymerase chain reaction and by flow cytometric analysis of TCRBV families. The CD4 and CD8 T-cell repertoire in most MDS patients is characterized by an abnormal TCRBV-restricted expansion of T cells in CD4 and CD8 cells, and increased expression of the CD8 effector marker CD57 of multiple TCRBV in CD8 cells. Clonality analysis of CD4 and CD8 cells showed that seven of 10 patients analysed had a major clone in the CD8 cells but not in CD4 cells. Furthermore, in one patient we found that both the CD57- and CD57+ fraction contained the clone (which was absent from the TCRBV-negative fraction). These data suggest that, in MDS, multiple T-cell expansions can be found in both helper and cytotoxic T cells, and that, in the CD8 cells, T cells functionally differentiate in vivo from memory to effector T cells. Together, these data support the hypothesis of the involvement of T cells in the pathogenesis of MDS.