To investigate the significance of peroxynitrite-mediated oxidative damage in the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS), the concentrations of 3-nitrotyrosine and tyrosine in the cerebrospinal fluid (CSF) of patients with SALS were determined. The concentration of 3-nitrotyrosine and the 3-nitrotyrosine/ tyrosine ratio in patients with SALS were approximately seven times those of controls. Thus, the present findings in living patients provide in vivo evidence for a possible role of peroxynitrite, a mediator of oxidative stress, and increased nitration of tyrosine residues in the pathogenesis of SALS.