Selegiline, a therapeutic agent of Parkinson's disease, is known to have neuroprotective properties that may involve its regulatory effects on antioxidant enzymes. We evaluated effects of selegiline on activities of catalase (CAT), Cu,Zn-superoxide dismutase (SOD1) and Mn-SOD (SOD2) in the striatum, cortex and hippocampus of 8- and 25-week-old rats, and on SOD activities and glutathione levels in mesencephalic slice cultures. Selegiline (2 mg/kg) significantly increased CAT and SOD2 activities in the striatum, but not in the cortex and hippocampus, of 25-week-old rats. In contrast, selegiline failed to increase CAT and SOD activities in three brain regions of 8-week-old rats, whereas L: -dopa significantly increased SOD1 activity in the striatum. In slice cultures, selegiline increased SOD1 and SOD2 activities with a maximal effective concentration of 10(-8) and 10(-10) M, respectively. Moreover, selegiline significantly increased glutathione level. These results suggest that selegiline can decrease oxidative stress in nigrostriatum by augmenting various antioxidant systems, each of which responds optimally to different concentrations of selegiline.