Localized proton magnetic resonance (MR) spectroscopy was used to define biochemical changes in gray and white matter of the cerebral cortex in 22 patients with diabetes mellitus (DM), including 10 episodes of diabetic ketoacidosis (DKA), compared with MR spectra in 30 healthy subjects. Five distinct metabolic abnormalities were identified: Concentrations of glucose (Glc) (P greater than or equal to .002), ketone body or bodies, myo-inositol (P greater than or equal to .003) (with or without glycine), and choline (Cho) metabolites were increased in both white and gray matter, whereas a significant reduction of N-acetyl metabolites was found in the parietal cortex (P greater than or equal to .003). Diurnal variations in the intracerebral concentration of Glc were demonstrated in a patient with DM whose condition was stable. Elevated concentrations of ketones were detected in three episodes and excess Cho in two episodes of DKA. Evidence obtained with hydrogen-1 MR spectroscopy favors acetone rather than acetoacetate as the ketone present in the brain, which is a major target of biochemical change in DM.