All subcortical afferents to the dorsal hippocampus, running in the fimbria-fornix and supracallosal path, were removed by aspiration. Three to 5 months later the rats were implanted with chronic recording electrodes in the dentate gyrus and CA1 region, and stimulating electrodes in the angular bundle. In non-lesioned rats, high-frequency trains delivered to the angular bundle gave rise to a sustained increase of the evoked population spike in the dentate gyrus. In lesioned animals, high-frequency stimulation resulted in only short-lasting changes, and by 15 min after the conditioning trains the amplitude of both the population spike and field postsynaptic potentials returned to baseline. In lesioned rats large amplitude interictal spikes (less than 40 ms, 3-8 mV) occurred spontaneously. These findings suggest that either (1) coactivation of entorhinal and subcortical inputs is essential for the induction of long-lasting plastic changes in the dentate gyrus, or (2) the long-term potentiation mechanism is saturated by the chronically occurring interictal discharges in the subcortically denervated dentate gyrus.