Background: Patients with chronic atopic dermatitis can become unresponsive to standard immunosuppressive therapy and thus pose a serious therapeutic problem. Objective: Our purpose was to evaluate the therapeutic effectiveness of photopheresis in the management of patients with severe and intractable atopic dermatitis. Methods: Photopheresis was used as monotherapy in patients (n = 3) who previously did not respond to treatment with glucocorticosteroids, cyclosporine, phototherapy, or photochemotherapy. Patients were treated at 2-week intervals (total number of treatments = 10). Results: In all patients, photopheresis induced clinical improvement and reduction of elevated serum levels of eosinophil cationic protein and total IgE. Prolongation of the intervals between treatments from 2 to 4 weeks caused worsening in one patient, whereas shortening of treatment-free intervals improved both clinical and laboratory findings. Conclusion: These studies indicate that photopheresis may be used as monotherapy for the treatment of patients with severe atopic dermatitis that has become intractable to standard therapeutic modalities. (J Am Acad Dermatol 1998;38:585-8.)