The extracellular concentration of glutamate in the neocortex of human brain may-increase progressively with ageing. Glutamergic nerve terminals seem to be a major source of the amino acid. There is no evidence that the concentration of extracellular glutamate is increased in the neocortex in Alzheimer’s disease. The few remaining neocortical cholinergic terminals in Alzheimer’s disease may be more metabolically active than those from normal brain. This is likely to be an adaptive change, unrelated to glutamate toxicity. Increased acetylcholine may itself be neurotoxic.