Background: Absence of CD7 antigen expression in T cells defines a subset of normal CD4⁺ CD45RO⁺ CD45RA⁻ memory cells and is furthermore observed in Sézary syndrome (SS). Objective: Our purpose was to identify circulating T-cell clones in patients with SS and to elucidate whether the dominant T-cell clones express the CD7 antigen. Methods: Peripheral blood lymphocytes of patients with SS were analyzed by two-color flow cytometry using antibodies to the Vβ region of the T cell receptor (TCR) in combination with an antibody to CD7. In addition, T cells were analyzed for TCR-γ gene rearrangement by polymerase chain reaction (PCR) techniques. Results: Clonal T-cell expansion was detected in 7 patients with SS by immunostaining of the TCR Vβ regions. PCR analysis confirmed the presence of dominant T cell clones. Double-immunostaining revealed that in each case cells of the clonal Vβ TCR rearrangement homogeneously express the CD4⁺CD7⁻ phenotype. Furthermore, CD4⁺CD7⁻ cells express the CD15s antigen but lack expression of CD26 and CD49d. Conclusion: Expansion of clonal T cells strongly correlates with the expansion of CD4⁺CD7⁻ T cells in 7 tested patients with SS. This supports our model that a subset of late differentiated, normal CD4⁺CD7⁻ memory T cells may represent the physiologic counterpart of Sézary cells. Monitoring of circulating T cells with the CD4⁺CD7⁻CD15s⁺CD26⁻CD49d⁻ phenotype proved to be useful for the identification of clonal T cells in patients with SS. (J Am Acad Dermatol 2001;44:456-61.)