Background: Because there are currently many effective therapies available for Sezary syndrome, close monitoring of disease progression is required in order for a clinican to know when to institute or change an intervention. It has been our clinical experience that changes in patients' CD4(+) CD26 T-cell populations of peripheral blood lymphoctes herald changes in their clinical status. Objective: Our purpose was to evaluate whether a change in patients CD4(+) CD26 population of T cells presages a change in their clinical status. We also sought to investigate the association between a change in T-cell populations that are CD4(+)CD7(-), CD8(+,) CD56(+), and the CD4(+) CD8(+) T-cell ratio and a change in the patients clinical status. Methods: We conducted a retrospective chart review analysis of 21 patients with Sezary syndrome who had flow cytometry, usually including levels of CD4(+) CD26(-), CD4(+)CD7(-), CD8(+), CD56(+), and CD4(+) CD8(+) ratios measured at two time periods, 12 weeks apart. Results: We report two cases in which changes in patients' clinical status were preceeded by several weeks by a change in their CD4(+) CD8(+) ratio and a worsening clinincal status. Limitations: The study was limited by the number of patients' and the time period over which the study was conducted. In addition, varying configurations of CD4(+) CD26. T-cell populations were observed that may have limited the utility of this measurement. Conclusions: Flow cytometry assays of patients' blood and in particular, measurement of the CD4(+) CD26 popoulation of lymphocytes over time may be a valuable tool for monitoring patients with Sezary syndrome. There exist varying configurations of CD26 T lymphocytes that may cause differences in standards for what is considered positive and negative between obserevers. Further prospective analysis involving larger groups of patients is recommended.