The levels of several low-molecular-weight metabolites were measured in 1H nuclear magnetic resonance (NMR) spectra of extracts of Syrian hamster brain infected with Creutzfeldt-Jakob disease (CJD). Metabolite levels were determined in cerebral cortex in CJD-infected and age-matched controls at defined times (40, 65, 85, 105, and 135 days) during the 130- to 135-day incubation period to terminal disease. At 135 days, CJD-infected hamsters showed a significant decrease in N-acetylaspartate of 32% (p < 0.05) and an increase in myo-inositol of 67% (p < 0.001) from age-matched controls. At earlier times (40 to 110 days) levels of N-acetylaspartate and myo-inositol were not significantly different from controls. No significant changes were detected in the cortical levels of glutamate, aspartate, or GABA between 40 and 135 days. The late changes in N-acetylaspartate and myo-inositol in CJD-infected hamsters are similar to those observed in magnetic resonance spectroscopy studies of human CJD. Because they also correspond to the changes found in other dementias, including Alzheimer's disease and HIV dementia, these changes indicate converging pathogenetic pathways involved in many neurodegenerative diseases.