Oxidative stress is implicated in the premature death of dopamine neurons in substantia nigra in Parkinson's disease. The incidence of Parkinson's disease is higher in men than in women, and estrogen may provide neuroprotection against oxidative damage. We examined the protective effects of estrogen on rat nigral death after chronic ozone inhalation. Ozone inhalation produced impaired nigral cell morphology and loss of dopamine neurons in ovariectomized rats. This was counteracted after 60 days of 17β-estradiol treatment, when blood levels were highest. These results indicate that ozone exposure may be a useful Parkinson's disease model and neuroprotection afforded by 17β-estradiol is dependent on the high levels achieved after its prolonged administration.