It has long been recognized that mesial temporal sclerosis is the most common pathologic finding in temporal lobes removed for the treatment of medically refractory complex partial epilepsy. The regions of the hippocampus most vulnerable contain the highest densities of excitatory amino acid receptors in the brain. We used receptor autoradiography to determine the density of N-methyl-D-aspartate (NMDA) and kainic acid (KA) receptors from 5 patients undergoing such surgery and compared the findings with 6 specimens obtained at postmortem. A 2-fold increase in the density of NMDA receptors and an increased density of KA receptors was found in entorhinal cortex in epileptic specimens. Loss of NMDA and KA receptor density was apparent in the sclerotic regions CA3 and CA1, but not in other areas of the hippocampus or dentate gyrus. These findings suggest that damage in the hippocampus may result, at least in part, from the presence of aberrant excitatory circuits in the entorhinal cortex.