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Oxidative stress is important in the process of dopaminergic neuronal degeneration in Parkinson's disease. Recent studies suggest that estrogens have neuroprotective effects in neurodegenerative disorders, including Alzheimer's disease. In the present study, we investigated neuroprotection against oxidative stress afforded by estradiol using primary neuronal culture of the rat ventral mesencephalon. Oxidative stress induced by glutamate, superoxide anions, and hydrogen peroxide caused significant neuronal death. Although simultaneous administration of 17β‐estradiol and glutamate did not show any significant effects, preincubation with 17β‐estradiol provided significant neuroprotection against glutamate‐induced neurotoxicity (ED₅₀ was 50 μM for dopaminergic and 15 μM for nondopaminergic neurons). Neuroprotection occurred even after a brief preincubation with 17β‐estradiol and was not significantly …