Background: Routine CD4/CD8 T-cell phenotyping may shows a small fraction of CD4dimCD8+ T cells with a homogeneous appearance as described for lymphoproliferative syndromes or chronic infections. The aim of this study was to elucidate the significance of CD4dimCD8þ T cells and their degree of diversity. Methods: Phenotyping was performed in 272 samples from healthy donors, elderly patients, and immunocompromised (human immunodeficiency virus or renal transplantation) patients. Results: The CD4dimCD8+ T cells had decreased fluorescence intensity for CD4 but not for CD8. The frequency of patients with CD4dimCD8+ T cells (>20 cells/ll; 10.3% of patients with human immunodeficiency virus and 7.7% with renal transplantation) was not significantly different when compared with healthy donors (9.7%). The CD4dimCD8+ T cells did not express the activation marker CD69. The CD8 of CD4dimCD8+ T cells expressed the heterodimeric (ab) isoform. In 13 of 26 samples, the apparently highly homogeneous CD4dimCD8+ T cells expressed one redominant T-cell receptor Vb clonotype. These predominant clonotypes were widely distributed among patients: Vb 5.2, 17, 2, 3, 5.1, 13.1, 14, and 20. Conclusions: Whether these findings demonstrate an oligoclonal reaction to chronic inflammation or an emerging lymphoproliferative disorder must be elucidated in a long-term longitudinal study. By analogy to monoclonal gammopathy, we propose to name this phenomenon ‘‘oligoclonal clonopathy of undetermined significance.''