A computer-assisted morphometric study has been carried out on ethanol phosphotungstic acid (E-PTA) stained synaptic junctions in the human dentate gyrus supragranular layer from adult, old and Alzheimer's disease (AD)-affected patients. The number of synapses per unit volume of tissue (Nv = numerical density), the average area of the single junction (S) and the total area of the synaptic contact zones in a unit volume of tissue (Sv = surface density) were the 3 parameters taken into account. The synapse to neurone ratio was also calculated for each patient. During physiological aging, Nv and Sv significantly decreased and S increased, respectively. In the AD hippocampi, Nv and Sv underwent a further decrease which was in the range of more than 40% with reference to the adult values. S was the same as the old control group. In comparison with the adult values, the number of synapse/neurone decreased by 15.6 and 48% in old and AD patients, respectively. Nv, S and Sv, while reporting on discrete ultrastructural features of the synaptic junctional zones, are closely related to each other and, taken together per group of patients, may represent a reliable index of the morphological adaptive changes taking place at the synapses. Thus, the significant increase of S both in old and AD hippocampi may be regarded as a CNS plastic response to aging and disease, although the marked decrease of Nv and Sv supports that in AD synaptic ultrastructural alterations proceed beyond a critical threshold for functional recovery.