To investigate the significance of nitric oxide (NO)-mediated neuron death in aging and Alzheimer's disease (AD), the 3-nitrotyrosine concentration in the cerebrospinal fluid (CSF) was investigated in neurologically normal controls and patients with AD. The 3-nitrotyrosine concentration and the 3-nitrotyrosine/tyrosine ratio significantly increased with advancing age, whereas the tyrosine concentration was unaltered. In patients with AD, the 3-nitrotyrosine concentration and the 3-nitrotyrosine/tyrosine ratio increased significantly (>six-fold) compared with controls of similar age, and increased significantly with decreasing cognitive functions, whereas the tyrosine concentration did not change. These findings suggest that an activation of tyrosine nitration, increase in nitrated tyrosine-containing proteins, and/or its degradation may be involved in brain aging and play an important role in the pathogenesis of AD.