Estrogens are thought to play a protective role against neurodegeneration through a variety of mechanisms including the activation of growth factors and neurotransmitter synthesis, the control of synaptic plasticity and functions, and the blockade of oxidative reactions. We here propose a novel mechanism to explain the neuroprotective effects of estradiol by showing that estrogens may antagonize nitric oxide synthase activity and reduce the accumulation of nitrites and nitrates consequent to various inflammatory stimuli.The potential anti-inflammatory activity of estradiol is analyzed in vitro in cells in culture including primary cultures of microglia and in vivo in a well-known model of inflammation.