A case-control study was designed to investigate a possible genetic susceptibility of the MTHFR C677T polymorphism and assess whether the genetic polymorphism could be a predictor of levodopa-induced adverse effects in patients with Parkinson's disease (PD) of Chinese descent living in Taiwan. There were 94 sporadic PD patients with levodopa therapy at least for five years and 146 control subjects, matched by sex and gender, in this study. Results revealed that there were no differences of the allelic and genotypic frequencies of the MTHFR C677T polymorphism between PD patients and the controls. Analysis of age at onset stratified by MTHFR C677T polymorphism showed a trend of early age at onset in the PD patients carrying with T allele. The genetic influence was particularly significant in late-onset PD (onset age at or older than 60 years) with an early age at onset for 3.4 years. However, the MTHFR C677T polymorphism was not associated with the risk to develop dyskinesia, motor fluctuation and psychosis induced by levodopa in PD patients. In conclusion, results of the study revealed that the MTHFR C677T polymorphism could significantly influence age at onset of PD in Chinese population, but neither as a genetic susceptibility nor as a predictor of levodopa-induced adverse effects in PD.