We initiated the present work in order to determine if the Ala53Thr mutation of the alpha-synuclein gene previously described by Polymeropoulos et al. [Science, 276 (1997) 2045-2047] could be detected in Spanish early onset Parkinson's disease (PD) patients. Thirty-four PD patients were evaluated. Of these, 13 were considered early onset patients (six familial and seven sporadic) and were included in the genetic study. We detected the presence of genetic anticipation in four kindreds with early onset PD members. The Ala53Thr mutation of the alpha-synuclein gene was absent in all patients. The results do not support a role for this mutation in our patients with early onset PD and, in agreement with the results previously reported, indicate that the Ala53Thr mutation of the alpha-synuclein gene is a rare cause of PD.