We studied two patients with Creutzfeldt-Jakob disease by in vivo proton magnetic resonance spectroscopy and obtained spectra from an extract of biopsy tissue from a third patient. In vivo spectra from the two patients, 3 months and less than 1 month after symptom onset, revealed only minor changes. A second study of one of the patients 10 months after symptom onset found a decrease in N-acetylaspartate and other metabolites. Spectroscopy of the biopsy extract obtained 4 months after onset of symptoms showed no reduction in metabolites measured by in vivo spectroscopy, in accord with quantitative pathology showing no overall neuronal loss. Changes in metabolites detectable by proton magnetic resonance spectroscopy are not an early feature of this disease.