The National Institute of Neurological Disorders and Stroke, Bethesda, Md, has approved a planning grant for a multicenter RCT of early surgical intervention for MTLE. Twelve epilepsy surgery centers are currently involved (Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, Ariz; Columbia Presbyterian Medical Center, New York, NY; Emory University School of Medicine, Atlanta, Ga; Massachusetts General Hospital, Boston; Southern California Permanente Medical Group, Los Angeles; Stanford University Medical Center, Stanford, Calif; Thomas Jefferson University Hospital, Philadelphia, Pa; University of California, Los Angeles, Medical Center, Los Angeles; University of Michigan, Ann Arbor; University of North Carolina, Chapel Hill; University of Rochester, Rochester, NY; and University of Texas Southwestern Medical Center, Dallas) and have already made progress in developing a common protocol. Patients aged 12 years or older who have had complex partial seizures for less than 2 years that have not responded to adequate trials of 2 antiepileptic drugs, one of which must be either carbamazepine or phenytoin, will undergo a standardized noninvasive presurgical evaluation. This will include inpatient video EEG monitoring to capture habitual seizures, MRI, positron emission tomography, and neurocognitive testing. Those patients diagnosed as having MTLE and considered to be surgical candidates will then be randomized to either a standardized anteromesial temporal resection or 2 additional years of pharmacotherapy. Detailed drug treatment protocols will be adhered to for patients in both the surgical therapy and pharmacotherapy arms. At the end of 2 years, the primary outcome measure will be a quantitative assessment of health-related quality of life. Secondary outcome measures will be seizure recurrence; objective indicators of social function, such as employment or school status, living conditions, and possession of a driver's license; cognitive function; psychiatric evaluation; mortality and morbidity; evidence of pathophysiological progression assessed with EEG and MRI hippocampal volumetry; and a cost-effectiveness analysis.