This study sets out to compare and contrast the astrocyte reaction in two unrelated experimental designs both resulting in marked chronic astrogliosis and natural motoneuron death in the wobbler mutant mouse and brain damage in the context of transplantation of xenogeneic embryonic CNS tissue into the striatum of newborn mice. The combined use of GFAP-labeling and confocal imaging allows the morphological comparison between these two different types of astrogliosis. Our findings demonstrate that, in mice, after tissue transplantation in the striatum, gliosis is not restricted to the regions of damage: it occurs not only near the site of transplantation, the striatum, but also in more distant regions of the CNS and particularly in the spinal cord. In the wobbler mutant mouse, a strong gliosis is observed in the spinal cord, site of motoneuronal cell loss. However, moderate astrocytic reaction (increased GFAP-immunoreactivity) can also be found in other wobbler CNS regions, remote from the spinal cord. In the wobbler ventral horn, where neurons degenerate, the hypertrophied reactive astrocytes exhibit a dramatic increase of glial fibrils and surround the motoneuron cell bodies, occupying most of the motoneuron environment. The striking and specific presence of hypertrophic astrocytes in wobbler mice accompanied by a dramatic increase of glial fibrils located in the vicinity of motoneuron cell bodies suggests that short astrogliosis fills the space left by degenerating motoneurons and interferes with their survival. In the spinal cord of xenografted mice, chronic astrogliosis is also observed, but only glial processes without hypertrophied cell bodies are found in the neuronal micro-environment. It is tempting to speculate that gliosis in the wobbler spinal cord, the local accumulation of astrocyte cell bodies, and high density of astrocytic processes may interfere with the diffusion of neuroactive substances in gliotic tissue, some of which are neurotoxic, and cooperate or even trigger neuronal death.