5-Hydroxytryptamine (5-HT) and choline acetyltransferase (ChAT) were assayed in amygdala, cingulate cortex and caudate nucleus of post-mortem brains from 7 cases of Down's syndrome (6 with the neuropathological features of Alzheimer's disease and one with no such features), 9 cases of Alzheimer's disease and 12 controls. 5-HT was markedly reduced in all 3 areas of the pathologically affected Down brains, unaltered in the Down brain with no Alzheimer pathology and reduced in the amygdala and cingulate cortex of the Alzheimer brains. ChAT showed a similar pattern of reduction. These results supply biochemical evidence that 5-hydroxytryptaminergic, as well as cholinergic, neurons are reduced in Down's syndrome with Alzheimer pathology.