Recent data suggest that amiotrophic lateral sclerosis (ALS) could be the result of motoneuron damage induced by endogenous or exogenous excitotoxins, and especially by excitatory amino acids (EAA). Three main sources support this hypothesis: 1) The induction of experimental models of motor neuron disease by 2 excitotoxins (BOAA and BMAA). 2) Evidence of disordered glutamate metabolism in ALS. 3) Data suggesting that EAAs may be a factor in the pathogenesis of other degenerative neurologic diseases (Huntington disease and Alzheimer disease). This new "excitotoxin hypothesis" of ALS is of particular interest as several effective antiglutamate agents are now available for human therapeutic trials.