In the present work we measured blood levels of total homocysteine (tHcy), vitamin B12 and folic acid in patients with Parkinson's disease (PD) and in age-matched controls and searched for possible associations between these levels with smoking, alcohol consumption, L-DOPA treatment and disease duration in PD patients. We initially observed that plasma tHcy levels were increased by around 30 % in patients affected by PD compared to controls. Linear correlation, multiple regression and comparative analyses revealed that the major determinant of the increased plasma concentrations of tHcy in PD patients was folic acid deficiency, whereas in controls tHcy levels were mainly determined by plasma vitamin B12 concentrations. We also observed that alcohol consumption, gender and L-DOPA treatment did not significantly alter plasma tHcy, folic acid and vitamin B12 levels in parkinsonians. Furthermore, disease duration was positively associated with tHcy levels and smoking was linked with a deficit of folic acid in PD patients. Considering the potential synergistic deleterious effects of Hcy increase and folate deficiency on the central nervous system, we postulate that folic acid should be supplemented to patients affected by PD in order to normalize blood Hcy and folate levels, therefore potentially avoiding these risk factors for neurologic deterioration in this disorder.