The pathophysiology of widespread interictal hypometabolism in temporal lobe epilepsy is unknown but might reflect neuronal loss and diaschisis. We found no significant correlation between any cortical region's metabolism on preoperative [18F]fluorodeoxyglucose positron emission tomography and neuronal density of resected hippocampi in 40 patients. We conclude that hippocampal neuronal loss and diaschisis cannot account for the regional interictal hypometabolism of temporal lobe epilepsy.