While many reports have documented the effects of hydrocephalus on the ependyma and periventricular white matter, primarily in adult animal models, little is known about alterations specific to neurons. The present study has evaluated qualitatively the effects of hydrocephalus on the neurons and vasculature of the cerebral cortex in a neonatal animal model. The cisterna magna of 4 to 11-day-old kittens was injected with a solution of 25% kaolin to induce hydrocephalus. Ultrasonographic evidence of hydrocephalus was noted within 3–5 days of injection. Hydrocephalus progressed until day 18–25 postinjection when the animals were sacrificed. The cytologic and cytoarchitectural changes within the cortical mantle of affected animals were compared with control age-matched counterparts who had undergone intracisternal saline injections. Areas 4 (primary motor), 22 (association) and 17 (primary visual sensory) were examined light microscopically. Neurons from hydrocephalic brains exhibited 3 types of pathological response. Pyknotic somata were shrunken, disoriented and so hyperchromatic that neither nuclei or nucleoli could be delineated. Reactive somata were also shrunken and hyperchromatic, but nuclei and nucleoli could still be observed. Many neurons contained an abundance of vacuoles, giving their somata a flocculent appearance; these cells were termed ‘spongy’ neurons. Both normal and pathological neurons were smaller and disoriented, with a considerable decrease in neurons noted in areas 22 and 17 from severely hydrocephalic animals. The deeper cortical layers were more affected than the more superficial laminae in that more reactive and pyknotic neurons were present in layers V and VI. As the ventriculomegaly became more severe, changes could be observed in neurons within layers II and III. Furthermore, the cerebral vasculature exhibited a decrease in the number of vessels and a preponderance of profiles oriented parallel to the menin-geal surface. The severity of these effects followed a rostral to caudal gradient, such that the occipital cortex demonstrated the most damage. These results suggest that both the motor deficits and the subtle cognitive deficiencies seen with hydrocephalus may be attributed to perturbation of neuronal and vascular elements in the cerebral cortex.