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 (1). Treatment has been palliative and includes corticosteroids, alkylating agents, antimetabolites, vinca alkaloids, and irradiation (2). 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 (5). Because tissue histiocytes are derived from the same stem cells as circulating monocytes, 2-CdA was a rational therapeutic option (6). We therefore administered 2-CdA to three patients with Langerhans-cell histiocytosis.