The accumulation of structural analogs of normal synaptic neurotransmitters (substitute or "false" neurotransmitters) can have profound behavioral and neurologic consequences. Such abnormalities of the metabolism of amines and amino acids may explain behavioral and neurologic changes in hepatic failure. Accumulations of substitute transmitters may mediate other neuropsychiatric phenomena in states of inborn or acquired metabolic error or after certain drugs associated with psychosis. In developing hypotheses concerning relationships between neuropsychiatric disorders and neurotransmitter metabolism, this mechanism might be considered as a novel approach.