In order to substantiate the hypothesis of a cholinergic pathogenesis of neuritic plaques in Alzheimer's disease the relationship between the loss of cholinergic neurons in six subdivisions of the nucleus basalis of Meynert and density of neuritic plaques in five neocortical target areas and hippocampus was studied in five cases with Alzheimer's disease. Distribution of plaques in different cortical areas as well as degeneration pattern of neurons within the subpopulations of the nucleus basalis were markedly different in the cases of Alzheimer's disease. Quantitative evaluation of the number of neuritic plaques in the five cortical areas revealed a strong correlation with the loss of neurons in those subpopulations of the nucleus basalis which give rise to the cholinergic innervation of the affected cortical areas. The nonlinearity of this correlation may reflect two different modes of plaque formation. Either plaque formation is a self-perpetuating process with an increasing rate depending on the number of plaques already formed or additional mechanisms, with an increasing rate of influence during plaque formation are induced. The shape of the regression function is different for the various cortical regions and their corresponding subpopulations of the nucleus basalis suggesting a different dependency of neuritic plaque formation on the neuronal loss in the nucleus basalis. This might reflect a different density of cholinergic fibers within these areas, a different degree of collateralization of the fibers or other factors not yet known. The findings indicate that degeneration of cortical cholinergic afferents from the neurons of the nucleus basalis is an important feature in the pathogenesis of neuritic plaques.