Langerhans' cell histiocytosis (LCH) (previously histiocytosis X) is an infrequent disease with protean clinical manifestations and an unpredictable course. The role of radiotherapy in the soft tissue complications of LCH was evaluated in this retrospective study of 40 patients seen in two major Philadelphia institutions between 1970 and 1984. The patients were divided into two groups according to the extent of disease: unifocal versus multifocal. There was a higher rate of complete response in the unifocal form (4 of 12 patients), but this was associated with a high rate of spontaneous remissions (6 out of 12 patients). Multifocal LCH has a more aggressive course, and the major organs involved (lung, liver, and spleen) did not respond to radiotherapy. Eight patients had diabetes insipidus, and none of them responded to radiotherapy or chemotherapy. Autopsies were performed in two patients with diabetes insipidus who died of disease. There were no pathologic changes in the pituitary gland or stalk, hypothalamus, or supraoptic nuclei.