Multiple system atrophy, a sporadic neurodegenerative disease, is characterized by the presence of high numbers of glial cytoplasmic inclusions mainly formed by α-synuclein protein, which is encoded by the SNCA gene. To date, however, few studies have investigated the plasma α-synuclein levels in patients with multiple system atrophy. We studied plasma α-synuclein concentrations by using an enzyme-linked immunosorbent assay in 74 patients with multiple system atrophy and 90 healthy controls. The plasma α-synuclein levels were significantly elevated in patients who had multiple system atrophy compared with the control group (P = 0.000). In a subgroup of 48 patients who had probable multiple system atrophy, there was a weakly negative correlation between plasma α-synuclein levels and subscores on Unified Multiple System Atrophy Rating Scale item VI (rs = −0.307; P = 0.034). Plasma α-synuclein levels were elevated in patients with multiple system atrophy, and these levels may be decreased with the development of disease. © 2013 International Parkinson and Movement Disorder Society.