Background: Extracorporeal photopheresis (ECP) has become a primary therapy for selected forms of cutaneous T-cell lymphoma, especially Sézary syndrome. Variability in response of patients with Sézary syndrome to ECP has been reported. Objective: Our purpose was to determine whether underlying medical conditions influence the efficacy of ECP in patients with Sézary syndrome. Methods: We retrospectively reviewed the medical records of 55 patients with Sézary syndrome who received ECP between 1987 and 2000. Efficacy criteria included decrease in Sézary cell count, erythroderma, lymphadenopathy, organomegaly, and pruritus. Results: Thirty-four patients responded well and 10 patients responded partially to ECP; 11 patients had no response. Nine patients with no response to ECP had insulin-dependent diabetes mellitus (IDDM). IDDM was documented in only 2 patients with a good response and in no patients with a partial response to ECP. Conclusion: Patients with Sézary syndrome and IDDM typically respond poorly to the standard ECP treatment regimen. (J Am Acad Dermatol 2002;47:63-7.)