Subacute encephalopathy developed in four patients within one to two months after undergoing high-dose chemotherapy and bone marrow transplantation or peripheral blood progenitor (stem) cell transplantation for breast cancer, acute myeloid leukemia, and non-Hodgkin's lymphoma. None of the patients had previously known neurologic disorders, central nervous tumor or infection. Two patients presented with generalized tonic, clonic seizures, and two with confusion and lethargy. In all patients lumbar puncture and CT scans of the brain were normal, while magnetic resonance imaging (MRI) demonstrated multifocal predominantly white matter lesions. Phenytoin therapy was given to the two patients with seizures and all four patients improved without specific therapeutic intervention. Repeat MRIs became normal within three months. We report a delayed and transient encephalopathy which appears to be a unique complication of high-dose cytotoxic chemotherapy. The corresponding brain lesions may not be appreciated on CT scans, suggesting an expanded role for MRI studies in patients who develop neurologic findings while undergoing high-dose cytotoxic therapy.