Sydenham's chorea (SC) is the neurologic manifestation of rheumatic fever. In addition to involuntary movements, SC patients show behavioral changes, such as hyperactivity, obsessions, and compulsions. Brain-derived neurotrophic factor (BDNF) is related to neuronal development and differentiation. Since BDNF serum levels are altered in a series of neuropsychiatric disorders, such as schizophrenia and Huntington's disease, we investigated the serum levels of BDNF in SC patients. Eighteen patients with acute SC, 4 with persistent SC and 27 control subjects were included in this study. BDNF was determined by ELISA. There was no significant difference between BDNF serum levels of control and acute SC groups (P = 0.12). Persistent SC patients presented decreased BDNF levels when compared to both control and acute SC groups (P < 0.001). Our results suggest that the persistence of symptoms in SC may be related to structural changes in the central nervous system as expressed by altered BDNF levels.