The activity of reduced nicotinamide adenine dinucleotide (NADH)-diaphorase was examined histochemically in the amygdala, cortex and sublenticular substantia innominata (nucleus basalis of Meynert) of patients with Alzheimer's disease and senile dementia of the Alzheimer type (SDAT). Senile plaques were characterized by increased enzyme levels and the presence of astrocytes highly reactive for NADH-diaphorase. In the sublenticular substantia innominata, the number of neurons positive for NADH-diaphorase was reduced in both Alzheimer's disease and SDAT, a result paralleled by a reduction of Nissl-stained cells, and this pathology was accompanied by an increase in the number of astrocytes. Intact substantia innominata somata in the former dementia, however, showed essentially normal levels of the enzyme, whereas in the SDAT patients, an abnormal distribution of NADH-diaphorase was observed frequently. It is proposed that the increased NADH-diaphorase associated with senile plaques and their accompanying astrocytes may be linked, in part, to the increased astrogliosis and decrease of neurons in the basal forebrain and that neuropathologic differences may exist between Alzheimer's disease and SDAT in terms of energy metabolism.