A quantitative morphometric analysis was used to estimate neurone and synapse densities in cerebral cortical biopsy tissues from patients with dementia under 65 years of age and pathologically verified as suffering from Alzheimer's disease. Estimates of the numerical density of neurones and synapses were made in layers II-III and V of both frontal and temporal cortex. A greater loss of synapses than that of neurones was found in Alzheimer's disease, amounting to a minimum (uncorrected for atrophy) of 25% in layers II-III and 36% in layer V of the temporal cortex, and 27% in layer V of the frontal cortex. Values of synapse to neurone ratio also demonstrated this greater loss of synapses, there being on average 38% fewer synapses associated with each surviving neurone in layers II-III of the temporal cortex, 30% fewer in layer V, and a deficit of 14% in layer V of the frontal cortex. It is concluded that a major loss of synapses occurred in this group of patients with Alzheimer's disease, probably at an early stage of the disease, and that the loss is likely to form a fundamental part of the pathological process that underlies the cortical damage of this condition.