The most important new development during recent years in the field of degenerative dementia concerns synaptic pathology. So far it has been investigated in some regions and some cortical laminae in Alzheimer''s disease (AD). The present communication is a more comprehensive study of all laminae in four different regions, the prefrontal, parietal, inferior temporal and posterior cingulate cortex. Against the background of normal aging, AD was compared with another degenerative disorder, frontal lobe degeneration of non-Alzheimer type (FLD). The synapse density was measured using synaptophysin as a marker. Astrocytes were also counted in the molecular layer. In normals, the cortex showed successively lower synaptic density from layer I to layer VI and relatively lowest density in the prefrontal cortex and a general decline with increasing age. A 46-49% decrease in synaptic density was found in all laminae in all regions of AD brains, a finding different from that in FLD. The number of astrocytes increased significantly in the prefrontal cortex both in AD and FLD but parietally only in AD. These results contribute to the understanding of normal synaptic organization of cortex, demonstrate the laminar and regional distribution of synaptic loss in AD and underscore the difference between AD and FLD. The gliosis appears to be secondary to the neurodegenerative changes. Synaptic loss is likely to be a common pathogenetic feature of neurodegenerative disorders and a likely cause of clinical symptoms and regional metabolic decrements in dementia.