We performed interictal [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in 17 patients with well-defined unilateral anterior mesial temporal epileptogenic foci as determined by EEG procedures. Sixteen of these patients subsequently underwent surgical resection of the epileptogenic focus. We measured local cerebral metabolic rates for glucose in mesial and lateral temporal structures and compared them with metabolic rates for analogous regions in 16 healthy normal volunteers and the contralateral hemisphere of the epileptic patients. We found relative hypometabolism ipsilateral to the seizure focus more frequently and to a greater degree in the lateral than in the mesial temporal cortex. Since the physiologic abnormalities involved mesial temporal structures, this observation suggests that functional pathways exist between mesial and lateral temporal cortex normally and that these pathways are altered in epilepsy of mesial temporal origin. Hypometabolism did not correlate well with histologic abnormalities in the surgical specimens.