Nine patients with multiple system atrophy (MSA) were studied based on MRI findings of cerebral hemispheric involvement. The age at onset was 56.4+/-8.6 (mean+/-S.D.) years, duration of illness at the first MRI study 2.1+/-1.1 years, duration of illness at the last study 9.7+/-2.6 years, and the follow-up duration 7.6+/-2.3 years. Controls were 85 neurologically intact persons (60.2+/-11.1 years age). In the MRI study, measurements of the ratio of each area to the intracranial area were performed for the cerebral hemisphere, frontal, temporal and parietal-occipital lobes. A significant progression of atrophy to under the normal limit was observed in the cerebrum, frontal and temporal lobes. Besides the typical pathological lesions in MSA, five autopsied patients revealed frontal lobe atrophy with mild gliosis, mild demyelination and glial cytoplasmic inclusions (GCIs). One of these patients showed remarkable frontal lobe atrophy with degenerative changes in the cerebral cortex. We observed the involvement of the cerebral hemisphere, especially the frontal lobe.