To investigate the significance of nitric oxide (NO) -mediated neuron death in aging and Alzheimer's disease (AD), the concentration of asymmetrical dimethylarginine (ADMA), an endogenous NO synthase inhibitor, in the cerebrospinal fluid was determined in neurologically normal controls and patients with AD. The ADMA concentration significantly decreased with age, whereas the arginine concentration was unaltered. In patients with AD, the ADMA concentration was significantly decreased, compared with controls of a similar age (-48%, P = 0.0001), and it significantly decreased with decreasing cognitive functions (r(s) = 0.58, P < 0.05), whereas the arginine concentration did not change. These findings suggest that ADMA may play an important role in regulating NO synthesis in brain aging and AD. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.