In the present study we performed a light microscopic anatomical comparison of adrenalectomy (ADX)-induced neurodegeneration using silver impregnation and reaction of astroglial cells using GFAP immunocytochemistry in the hippocampus of the rat. Three survival times following ADX were studied: 24 hours, 3 days, and 3 weeks. Twenty-four hours following ADX we found no degenerative changes or altered GFAP immunostaining. Three days after adrenalectomy, argyrophilic somata appeared in the granular cell layer of the dentate gyrus. Argyrophilic dendrites were seen in the molecular layer of the dentate gyrus and neuritic argyrophilia were seen in the mossy fiber layer. Induction of GFAP immunoreactivity occurred simultaneously with degeneration. Increased GFAP immunoreactivity could be observed 3 days after adrenalectomy in the molecular layer of the dentate gyrus, granular cell layer, sub and supragranular cell layer, and mossy fiber layer. Size and shape of astroglial cells were changed, and their processes in the molecular layer changed from unidirectional to randomly organized. Degeneration and astroglial reaction were more pronounced 3 weeks after adrenalectomy and both were prevented by adding corticosterone to the drinking solution. Animals that did not show degenerative changes showed no increased GFAP immunoreactivity, while both effects were confined to the dentate gyrus and mossy fiber zone. These results show that there is a close relationship between the induction of GFAP immunoreactivity in the hippocampus of the rat and neuronal degeneration in the dentate gyrus following ADX, both in time and space. © 1994 Wiley-Liss, Inc.