At the present time, it seems unlikely that progressive neurodegenerative diseases, such as ALS, Parkinson's disease, and dementia of the Alzheimer type, are triggered by environmental agents with excitotoxic potential. These include excitotoxic agents that behave as glutamate agonists or disrupt energy metabolism: both types elicit permanent but self-limiting neuronal diseases with patterns of neuronal deficit that reflect selective chemical exposure (MPP+ and parkinsonism), differential susceptibility to energy dysmetabolism (NPA and dystonia), or the distribution of glutamate-receptors (domoic acid and memory loss). If environmental agents play an etiologic role in progressive neurodegenerative diseases, they are likely to target a critical, irreplaceable neuronal molecule that is required to maintain long-term neuronal integrity.