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Background Multiple system atrophy (MSA) is a sporadic neurodegenerative disease. According to the clinical presentation a parkinsonian type and a cerebellar type (MSA-C) are distinguished. Objective To study the morphological alterations of MSA-C–affected brains in vivo using voxel-based morphometric analysis of magnetic resonance images. Setting University hospital. Patients Fourteen patients (5 men and 9 women) with MSA-C (mean age [SD], 59.4 [7.4] years; mean [SD] disease duration, 3.7 [1.4] years) and 13 healthy control subjects (5 men and 8 women) (mean [SD] age, 55.1 [6.9] years) were studied. Methods T1-weighted magnetic resonance images were normalized to a common stereotaxic space and segmented into gray and white matter. Data were analyzed using statistical parametric mapping (SPM99). Results Gray matter was reduced in the brainstem and the anterior lobe of the cerebellum. Reduction of white matter was observed in the middle cerebellar peduncles, cerebellar white matter, and brainstem. The inverted comparison revealed an increase of white matter density along the pyramidal tracts. Conclusions Voxel-based morphometry revealed a significant loss of cerebellar and brainstem tissue in MSA-C. It allowed a precise anatomical localization and a distinction between gray and white matter densities. In addition, our data point to a particular involvement of the pyramidal tract in MSA-C.