Sustained stimulation of the perforant pathway (PP) offers a model for studying seizure-induced pathology of the hippocampal formation. Using quantitative autoradiography, NMDA-sensitive glutamate binding was evaluated in the rat hippocampus three weeks after PP-stimulation. Decreased receptor binding (38-44%) was found together with pyramidal cell damage and gliosis in the CA1 area, ipsilateral to the stimulation (p < or = 0.001). In the dentate gyrus, however, a 20% increase in receptor density was observed bilaterally within the molecular layer (significant within the outer molecular layer of the contralateral side, on the suprapyramidal location; p < or = 0.05). These results are similar to those found in epileptic patients and suggest a prominent role for NMDA receptors in epilepsy.