The aim of this study was to compare patients with Parkinson disease (PD) patients treated with pergolide mesylate (PM), a dopaminergic receptor agonist, together with L-DOPA and those these treated with L-DOPA alone on the concentration of free radicals (FR), glutathione, and the activity of superoxide dismutase (SOD) and catalase in the serum. The study was carried out using 16 age-matched control subjects, 16 PD patients treated with L-DOPA at a dose of 1 to 1.5 g daily, and 16 PD patients treated with L-DOPA 1 to 1.5 g daily with PM 0.75 to 1.25 mg daily. The mean duration of treatment of PD was 6 years (range, 2-8 years) with l-DOPA, and 2 years with PM + L-DOPA or L-DOPA alone. Although there was no significant difference in lipid peroxidation products among the 3 groups, patients treated with L-DOPA showed high levels of FR as determined by dichlorofluorescein. Although catalase and SOD activities were elevated in both groups of PD patients, additional treatment with PM further enhanced catalase activity compared with those treated with l-DOPA alone. Interestingly, patients treated with PM + L-DOPA showed a significantly increased level of glutathione compared with those treated with L-DOPA alone. Collectively, these data suggest that PM + L-DOPA is a more efficient therapy in maintaining an antioxidative defense in PD patients compared with treatment with L-DOPA alone.