We used positron emission tomography (PET) to characterize cerebral metabolism in 7 patients (serial examinations in 2 patients) with central nervous system disease in Langerhans cell histiocytosis (CNS-LCH) who had neuroendocrine abnormalities (n = 7), neuropsychiatric disabilities (n = 3), and CNS degenerative disease (n = 1). The PET scan alterations occurred at localizations with known CNS-LCH disease. The PET scans revealed areas where the metabolism and function were altered in 6 of the 7 patients studied, with either an increased or a decreased metabolism (uptake of glucose). Serial examinations may indicate alterations in the degree of ongoing disease activity, but further studies on functional imaging are desired. The additional information of PET compared with MRI is the ability to detect alterations in CNS metabolic activity in certain patients with CNS-LCH. PET may also provide a tool for longitudinal follow-up of therapeutic measures in selected patients.