Two patients with malignant brain tumors who developed acute nonlymphocytic leukemia after treatment with radiation and chemotherapy are described. Both patients survived more than 2 years after diagnosis of the brain tumor. Survival following the diagnosis of leukemia was short, and both patients died of hemorrhage secondary to thrombocytopenia. A review of the literature reveals that leukemia after combined-modality treatment of malignant brain tumors is rare. A prolonged survival period from diagnosis of the primary tumor, treatment with nitrosoureas and radiation, plus the development of a preleukemic myelodysplastic syndrome are all important features of therapy-related nonlymphocytic leukemia.