In this study, we performed in situ hybridization analysis of the expression pattern of two growth-associated proteins, stathmin and SCG10, in the hippocampus after unilateral lesion of the perforant pathway, the main excitatory input from the entorhinal cortex to the hippocampus. Stathmin is one of the major neural-enriched cytosolic phosphoproteins and a potential target of cyclic-AMP-dependent kinases [Jin L. W. et al. (1996) Neurobiol. Aging 17, 331-341; Leighton I. A. et al. (1993) Molec. Cell Biochem. 127/128, 151-156]. Three days after the lesion, stathmin messenger RNA was up-regulated ipsilaterally in the hilus, in the granule cell layer of the dentate gyrus and in the pyramidal cell layer of the CA1 region. Simultaneously, the hilar region of the contralateral dentate gyrus showed an increased stathmin messenger RNA expression. This altered expression pattern was observed until 15 days after lesion. Stathmin messenger RNA expression returned to a normal level until 21 days after lesion in all regions analysed. SCG10, a membrane-bound neuronal growth-associated protein belonging to the SCG10/stathmin gene family, did not show any alteration of messenger RNA expression after perforant path lesion. The temporal changes of stathmin messenger RNA expression in the ipsilateral hippocampus correspond well to the process of reactive synaptogenesis. The enhanced messenger RNA expression in the hilar region of the contralateral dentate gyrus might suggest a role in neurite elongation, since this region is the origin of commissural fibres involved in the sprouting response in the deafferented hippocampus. The present study provides evidence that the induction of specific growth-associated proteins is differentially regulated in the hippocampus.