Intraventricular injections of kainic acid were used to destroy the hippocampal CA3-CA4 cells, thus denervating the inner third of the molecular layer of the fascia dentata and stratum radiatum and stratum oriens of area CA1. The responses of intact afferents to such lesions were then examined histologically. The hippocampal mossy fibers densely reinnervated the inner portion of the dentate molecular layer after bilateral destruction of CA4 neurons and to a lesser extent after unilateral destruction. Septohippocampal fibers replaced CA4-derived fibers in the dentate molecular layer only after particularly extensive bilateral CA4 lesions. Medial perforant path fibers showed no anatomical response to any of these lesions. Neither septohippocampal, temporoammonic nor mossy fibers proliferated in or grew into the denervated laminae of area CA1. These results show a preferential ordering in the reinnervation of dentate granule cells which is not readily explained by proximity to the degenerating fibers and also that removal of CA3-CA4-derived innervation more readily elicits translaminar growth in the fascia dentata than in area CA1. These results may be relevant to clinical situations in which neurons of the hippocampal end-blade are lost.