Concentrations of glutamic acid have been reported to be elevated in fasting plasma and cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS); glycine concentrations have also been reported to be increased in the CSF of such patients. Autopsy studies have shown glutamate contents to be significantly decreased in brain and spinal cord in ALS. These observations suggested that a systemic abnormality of glutamate metabolism might underlie the pathogenesis of ALS. We report here the findings of our studies of amino acid concentrations in patients with the sporadic form of ALS. Glutamate concentrations were normal in the fasting plasma of a great majority of the patients with ALS. Concentrations of glutamate, aspartate, and glycine were normal in the CSF of all 17 patients examined. beta-N-Methylamino-L-alanine, a plant neurotoxin possibly responsible for causing the Guamanian form of ALS, was not detectable in the plasma or CSF of any of our patients. Our findings do not lend support to the hypothesis that the sporadic form of ALS results from overexcitation of motor neurons by excitatory amino acids.