We evaluated S100B protein and neuron-specific enolase (NSE) serum levels in Parkinson's disease (PD) patients and their correlation with the severity of disease. The levels of S100B (P=0.16) and NSE (P=0.39) between PD and controls were similar. However, S100B levels correlated positively with the Hoehn and Yahr scale (r=0.368; P=0.02) and negatively with the Activities of Daily Living (ADL) scale (r=-0.431; P=0.006). Therefore, S100B and NSE may not have a diagnostic role in PD, but S100B may have a potential role as a marker of disease progression. The study of S100B may also contribute to elucidate the controversial role of glial cells in PD.