We used spin-echo magnetic resonance imaging and prton magnetic resonance spectroscopic imaging in 8 patients with probable Alzheimer's disease and in 10 age-matched elderly control subjects to assess the effects of Alzheimer's disease on the brain. On magnetic resonance images the patients showed signficant ventricular enlargements relative to the control subjects. We measured the distribution and relative signal intensities of N-acetylaspartate (a putative neuronal marker), of choline residues representing lipid metabolities, and of creatine-containing metabolites in a large section of the centrum semiovale containing white and mesial gray matter. Throughout the white matter of the patients with Alzheimer's disease compared to elderly control subjects, N-acetylaspartate was decreased relative to choline (N-acetylaspartate–choline ration) and creatine-containing metabolities (N-acetylaspartate–creatine ratio) with no changes in the choline-creatine ratio. The N-acetylaspartate–choline ratio was lower and choline-creatine higher in the mesial gray matter of AD patients relative to elderly controls. The posterior section of the centrum semiovale in the patients showed increased choline-creatine and choline–N-acetylaspartate ratios with the N-acetylaspartate–creatine ratio unchanged between the patients and control subjects. These spectroscopic findings give suggestive evidence of diffuse axonal injury and membrane alterations in gray and white matter of the centrum semiovale in patients with Alzheimer's disease.