This study demonstrates that the removal of a major hippocampal afferent system, the fibers from the entorhinal cortex, results in transneuronal changes in postsynaptic GABAergic inhibitory neurons. Following swelling of their distal segments, the peripheral dendrites of these cells retract from the termination zones of degenerating entorhinal fibers in the outer molecular layer of the fascia dentata and in stratum lacunosum-moleculare of the hippocampus proper. These dendritic alterations are long-lasting and do not seem to be restored by sprouting of other intact afferents. Persisting transneuronal changes in GABAergic hippocampal neurons following the removal of their entorhinal afferents may play a role in Alzheimer's disease since there is a severe degeneration of the entorhino-hippocampal projection in this neurodegenerative disorder.