Cushing's disease developed in a 5-year-old girl with acute lymphoblastic leukemia 18 months after her last therapeutic exposure to adrenal glucocorticosteroids. Obesity, hyperpigmentation, striae, osteoporosis, and hirsutism were accompanied by elevated levels of plasma cortisol. These showed no diurnal fluctuation and they were not suppressed by dexamethasone. At autopsy, the adrenal glands were enlarged and the pituitary gland showed increased numbers of basophils of the adrenocorticotropic hormone (ACTH)/melanocyte-stimulating hormone secreting type. Leukemic infiltrates in brain tissue were prominent in the hypothalamus and in the limbic system. It is postulated that the destructive leukemic infiltrate of the limbic system removed a restraining influence on pituitary function, with basophilic hyperplasia, ACTH hypersecretion, adrenocortical hypertrophy, and clinical Cushing's disease the consequences.