Subacute sclerosing panencephalitis is reported in a 16-year-old girl with a 2 1/2-year history of right-sided simple partial sensory and motor seizures. The seizures were verified with video-electroencephalographic monitoring, showing left frontal epileptic activity. After an initial response to antiepileptic medication, her seizures became intractable, and mild, right-hemisphere signs developed. Magnetic resonance imaging showed an extensive right-hemisphere infiltrative lesion, thought to be a neoplasm. Cortical brain biopsy raised the possibility of subacute sclerosing panencephalitis, and this was confirmed serologically. The case highlights the importance of considering subacute sclerosing panencephalitis in the differential diagnosis of intractable seizures and demonstrates that strikingly asymmetrical magnetic resonance imaging abnormalities are not inconsistent with this diagnosis.