Motor and cognitive deficits are commonly associated with hydrocephalus. Although the mechanisms responsible for these impairments have not been confirmed, neuronal cell death and axon degeneration may play an important role, and have long lasting consequences on neuronal connectivity. The goal of this study was to determine if neural degeneration occurred during hydrocephalus in structures anatomically related to cognitive motor functioning, namely, the sensorimotor cortex, neostriatum, hippocampus and corpus callosum. Neural damage, as visualized by silver staining, was examined in adult rats 2-10 weeks after obstructive hydrocephalus was induced by kaolin injection into the cisterna magna. In mild or moderate hydrocephalus, mostly occurring 2-6 weeks after kaolin injections, silver-labeled axons were scattered in the white matter of the sensorimotor cortex, corpus callosum, neostriatum, and hippocampus. In severe hydrocephalus, 10 weeks after kaolin injections, axon degeneration was more extensive in these areas, as well as in layers IV through VI of the sensorimotor cortex. Axons in the subiculum and the fimbria were heavily labeled, suggesting damage to hippocampal afferent and efferent fibers. In contrast, neuron cell death was rarely observed at any stage of hydrocephalus. The major pathological change of brain regions involved in motor and learning functions during hydrocephalus is axon degeneration, and this degeneration is correlated with an enlargement of the cerebral ventricles.