Septal and entorhinal projections to the hippocampus show a considerable overlap in their target structures in the molecular layer of the dentate gyrus (DG) and stratum lacunosum-moleculare of the cornu ammonis (CA). Employing anterograde tracing methods, it was investigated in which way the morphological pattern of the septohippocampal projections were influenced by lateral entorhinal cortex (LEA) lesions. Anterograde filling of neurons from soma to axonal terminals with Phaseolus vulgaris leucoagglutinin (PHA-L) revealed lesion-induced changes in innervation patterns in the DG but not in CA fields. LEA lesions provoke an impressive shift of septo-dentate projections from a predominant middle molecular layer innervation to the outer molecular layer, whereas septal projections to the CA remain unchanged. Comparison with concurrent acetylcholinesterase (AChE) staining and immunocytochemical demonstration of choline acetyltransferase (ChAT) confirm the cholinergic nature of this plasticity response. This response was equally strong in unilateral or bilateral damage to the LEA and was neither enhanced nor inhibited by simultaneous injury to the median raphé nuclei.