In rat brain, calcification associated with excitotoxicity has been proposed to play a protective role, whereas in human brain, nonartherosclerotic calcification is present in several pathological conditions without any clear significance. To determine if calcification can be viewed as a protective step of calcium homeostasis during chronic and acute neuronal suffering, cerebral cortex and hippocampus of patients with Alzheimer's disease, vascular dementia and neonatal hypoxia-ischemia were investigated. To investigate the human specificity, these two areas were also studied in dogs with established cognitive deficits. In all groups, calcium precipitates were observed in the cerebral parenchyma associated with neuronal damage. The cerebral cortex presented a higher degree of calcification than the hippocampus. The neonatal hypoxia-ischemia group was characterised by a higher degree of calcification, whereas the groups with lowest calcification were the Alzheimer's patients and dogs. As shown by X-ray microanalysis, in the precipitates, calcium is mainly associated with phosphorus in a form that resembles hydroxyapatites. Thus, intracellular calcium concentration associated with neuronal suffering may reduce the energy extrusion. We propose that, to help overcome excitotoxicity, calcium precipitation acts in CNS of vertebrates as a new compartment of the calcium homeostasis in which free cytoplasmic calcium ions are inactivated by phosphate ones.