The pathophysiology of infantile hydrocephalus is poorly understood, and shunt treatment does not always lead to a normal neurological outcome. To investigate some of the neurochemical changes in infantile hydrocephalus and the response to shunt treatment, we have used high-resolution 1H-NMR spectroscopy to analyze extracts of cerebral cortex from H-Tx rats, which have inherited hydrocephalus with an onset in late gestation. Hydrocephalic rats and rats with shunts placed at either 4 or 12 days after birth were studied at 21 days after birth, together with age-matched control littermates. In hydrocephalic rats there was a 46-62% reduction in the following compounds: myo-inositol, creatine, choline-containing compounds, N-acetyl aspartate, taurine, glutamine, glutamate, aspartate, and alanine. Phosphocreatine, glycine, GABA, and lactate were also reduced but not significantly. These changes are consistent with neuronal atrophy rather than ischemic damage. In hydrocephalic rats that received shunt treatment at 4 days, there were no significant reductions in any chemicals, indicating a normal complement of neurons. However, some compounds, particularly taurine, were elevated above control. After treatment at 12 days, N-acetyl aspartate and aspartate remained significantly reduced, suggesting continued neuronal deficiency.