THE hippocampi of epileptic patients with medial temporal lobe epilepsy exhibit a characteristic pattern of anatomical changes including cell loss and sprouting of the granule cell axons, the mossy fibers, into the inner molecular layer of the dentate. In addition to glutamate, mossy fibers release Zn2+. In the present study we investigated the action of Zn2+ on excitatory synaptic potentials in the dentate granule cells of patients wkh medial temporal lobe epilepsy. We show here that Zn2+ limits the duration of excitatory responses in these cells, probably by blocking the N-methyl-D-aspartate (NMDA) receptors. Zinc may, therefore, play an important role in limiting epileptiform activity in this tissue.