Both methylenetetrahydrofolate (MTHFR) C677T genotype and levodopa treatment may give rise to elevated serum homocysteine levels in parkinsonian patients. We aimed to clarify the interplay of these factors in pathogenesis of Parkinson's disease (PD)-related hyperhomocysteinemia. Total serum levels of homocysteine (tHcy) and MTHFR C677T genotype were investigated in levodopa-treated and -untreated parkinsonian ("de novo") patients, as well as in control healthy subjects matched by age and gender (N=83, 30 and 53, respectively). MTHFR C677T genotypes were equally distributed in PD patients and control subjects, the T allele homozygosity being observed in app. 12-17% cases. tHcy concentrations were significantly higher in both levodopa-treated and -untreated PD patients than in control subjects, and in TT homozygotes than in CT or CC genotype carriers. tHcy levels significantly correlated with the duration of the disease in PD treated patients only, reaching the maximum after 3-6 years. However, there was no correlation between tHcy levels and total daily intake of levodopa in the same group of PD patients. In conclusion, MTHFR C677T genotype is a significant factor for hyperhomocysteinemia in patients with PD, levodopa-untreated and probably even more in levodopa-treated PD patients.