Langerhans-cell histiocytosis results from the proliferation and accumulation of tissue histiocytes, clinically manifested as osteolytic lesions, hypothalamic insufficiency, and seborrheic and vesiculopustular lesions on the scalp, perineum, rectum, and vulva . Treatment has been palliative and includes corticosteroids, alkylating agents, antimetabolites, vinca alkaloids, and irradiation . Combination chemotherapy offers no advantage over the use of single agents and is associated with greater toxicity. 2-Chlorodeoxyadenosine (2-CdA) (cladribine, Leustatin [Ortho Biotech, Raritan, New Jersey]), a purine analog with activity in indolent lymphoproliferative disorders and myeloid leukemias [3–4], is potently toxic to monocytes in vitro . Because tissue histiocytes are derived from the same stem cells as circulating monocytes, 2-CdA was a rational therapeutic option . We therefore administered 2-CdA to three patients with Langerhans-cell histiocytosis.