Multiple system atrophy (MSA) is a sporadic neurodegenerative disease with unknown etiology, involving Parkinson's disease, Autonomic Failure, and Olivopontocerebellar Atrophy (OPCA). To define a possible relationship between phagocytic immune cells and loss of Purkinje cells in MSA/OPCA, we measured the incidence of microglial/macrophages in close association with Purkinje cells and/or their axons and dendrites. Using immunocytochemistry methods on cerebellar sections from MSA and control brains from the New York Brain Bank at Columbia University, we identified Purkinje cells and their processes using anti-calbindin, and microglia/macrophages using anti-CD68. Calbindin labeled Purkinje cell body, axon, and dendritic profiles were counted in the Purkinje cell layer, adjacent granule cell layer, and molecular layer respectively, as were calbindin stained profiles double labeled with CD68. The relative area of calbindin labeled axons and axons double labeled with CD68 in white matter tracts adjacent to the granule cell layer was measured using computer assisted image analysis. MSA/OPCA showed significantly fewer Purkinje cell bodies (ANOVA, p=0.001), dendrites (p=0.044), and axons (granule cell layer, p=0.002; nerve tracts, p=0.027) compared to controls. A significantly greater density of microglia/macrophage staining associated with calbindin stained profiles occurred only in the nerve tracts (p=0.043) compared to controls. Thus, although MSA/OPCA shows fewer Purkinje cell related profiles in all foliar areas, no clear association with phagocytic cells is evident except in the white matter tracts. This is compatible with other work showing an association between phagocytic cells and myelin loss in fiber tracts in MSA/OPCA. The decrease in Purkinje cell profiles does not appear to be due to an autoimmune interaction with phagocytic cells aimed at Purkinje cell antigens, rather it may related to loss of myelin caused by interactions between phagocytic cells and myelinating oligodendrocytes.