We used proton magnetic resonance spectroscopic imaging (1H-MRSI) to assess the in vivo cortical and subcortical neuronal involvement in progressive supranuclear palsy, Parkinson's disease and corticobasal degeneration. This technique permitted the simultaneous measurement of compounds containing N-acetylaspartate (NA), choline (Cho), creatine-phosphocreatine (Cre) and lactate, from four 15-mm slices divided into 0.84-ml single-volume elements. The study included 12 patients with progressive supranuclear palsy, 10 with Parkinson's disease, nine with corticobasal degeneration and 11 age-matched normal control subjects. Regions of interest were selected from the brainstem, caudate, thalamus, lentiform nucleus, centrum semiovale, and from frontal, parietal, precentral, temporal and occipital cortices. Progressive supranuclear palsy patients, compared with control subjects, had significantly reduced NA/Cre in the brainstem, centrum semiovale, frontal and precentral cortex, and significantly reduced NA/Cho in the lentiform nucleus. Corticobasal degeneration patients, compared with control subjects, had significantly reduced NA/Cre in the centrum semiovale, and significantly reduced NA/Cho in the lentiform nucleus and parietal cortex. There were no significant differences between Parkinson's disease patients and control subjects, or between patients groups in any individual region of interest. In the parietal cortex of corticobasal degeneration patients, NA/Cho was significantly reduced contralateral to the most affected side. There were statistically significant group differences in the regional pattern of NA/Cre and NA/Cho reduction, comparing normal control subjects with all patient groups, Parkinson's disease with corticobasal degeneration, and Parkinson's disease with progressive supranuclear palsy. Although the occurrence of significant groups differences does not imply that it is possible to differentiate between individual patients using 1H-MRSI in progressive supranuclear palsy and corticobasal degeneration, detection of specific cortical and subcortical patterns of neuronal involvement is possible with this technique. We suggest that this regional pattern of neuronal involvement found in progressive supranuclear palsy and corticobasal degeneration may help in the diagnostic evaluation of affected individuals.