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Parkinson's disease is characterized by the mesencephalic dopaminergic neuronal loss, possibly by apoptosis, and the prevalence is higher in males than in females. The estrogen receptor (ER) subtype in the mesencephalon is exclusively ER β, a recently cloned novel subtype. Bound with estradiol, it enhances gene transcription through the estrogen response element (ERE) or inhibits it through the activator protein‐1 (AP‐1) site. We demonstrated that 17 β‐estradiol provided protection against nigral neuronal apoptosis caused by exposure to either bleo‐mycin sulfate (BLM) or buthionine sulfoximine (BSO). BLM and BSO‐induced nigral apoptosis was blocked by inhibitors for caspase‐3 or c‐Jun/AP‐1. The antiapoptotic effect by estradiol was blocked by ICI 182,780, an antagonist for ER, but not by a synthesized peptide that inhibits binding of the ER to the ERE. Estradiol had no effects on caspase‐3 activation …