Background: Peripheral eosinophilia occurs in a small subpopulation of patients with cutaneous T-cell lymphoma (CTCL) and denotes a poor prognosis. Clinical studies have suggested that the Sézary cell is a T_H2 type helper T cell that produces cytokines that enhance the differentiation and activation of eosinophils. Interferon alfa (IFN-⍺) and interleukin 12 are effective therapeutic agents for CTCL and other hematologic disorders. Objective: Our purpose was to determine the inhibitory activity of IFN-⍺ and IL-12 on IL-5 production in vitro by peripheral blood mononuclear cells (PBMCs) obtained from patients with CTCL and eosinophilia. Methods: Suppression of IL-5 production by IFN-⍺ and IL-12 was assessed by comparing IL-5 production by PBMCs from patients with Sézary syndrome and eosinophilia when cultured alone or in the presence of either IFN-⍺ or IL-12. Results: A marked increase in IL-5 production by PBMCs from patients with Sézary syndrome and eosinophilia was observed. IL-5 production was markedly reduced when PBMCs were exposed to IFN-⍺ or IL-12. Conclusion: These results suggest that IFN-⍺ and perhaps IL-12 may produce a therapeutic response in patients with CTCL and eosinophilia through direct suppression of IL-5 production by malignant Sézary cells. (J Am Acad Dermatol 2001;44:28-32.)