By using flow cytometry with markers for CD3, CD4, CD26, and CD7, we examined the blood samples of 109 patients for abnormal T cells: 69 patients with mycosis fungoides (MF)/Sézary syndrome (SS), 31 hospitalized control subjects, and 9 patients with inflammatory skin disease. T cells were identified as quantitatively abnormal (>15% CD26- or CD7- T cells) or phenotypically abnormal (CD26- or CD7- T cells with bright or dim CD3 or CD4 or bright CD7). Patients were followed for a median of 82 months, and abnormal T cells were correlated with diagnosis, clinical outcome, and other laboratory parameters. Abnormal T-cell populations were identified in 46% of patients with MF/SS (32/69) and correlated with disease extent. Quantitative abnormalities were more frequent than phenotypic abnormalities, and CD4+/CD26- T cells were more frequent than CD4+/CD7- T cells. CD26- T cells correlated better with disease extent than did CD7 -. Increasing numbers of abnormal T cells were associated with worsening disease. Flow cytometry provides valuable information for diagnosis, prognosis, and therapeutic efficacy in MF/SS.