Free radicals and oxidative stress have been suggested in the pathogenesis of Parkinson's disease (PD). Free radicals exert their cytotoxic effect by peroxidation of lipid membrane resulting in the formation of malondialdehyde (MDA). This condition has been found to occur in the substantia nigra (SN). The present study was designed to investigate whether oxidative stress extended beyond the CNS. Therefore, the levels of lipid peroxidation and tocopherol in plasma and erythrocytes of the patients were measured. Twelve idiopathic PD patients with early or non-motor fluctuation (NF-PD), ten idiopathic patients with severe motor fluctuations (MF-PD), and seventeen age-matched healthy subjects (NM), were included in this study. The lipid peroxidation was determined by thiobarbituric acid test and reported as thiobarbituric acid reactive substance (TBARS), and the level of tocopherol was determined by HPLC. The results showed that the plasma TBARS was significantly increased in MF-PD patients compared to control group (0.721 ± 0.124 and 0.538 ± 0.124 nmol/ml respectively, p <0.05) but not NF-PD group (0.662 ± 0.156 nmol/ml). There was no significant difference between NFPD patients and control group. The erythrocyte susceptibility to hydrogen peroxide inducedautoxidation, as well as the level of tocopherol in plasma and erythrocytes were not significantly different among the three groups. The correlation between ages of the patients, the duration of disease and those markers were not evident in this study, but there was positive relationship between severity of the disease manifested as motor fluctuation and plasma TBARS. Our finding clearly indicated that oxidative stress was present in systematic circulation of PD patients with severe motor fluctuations and it was tissue specific.