Recent evidence indicates that an impairment of neuronal adaptive and reparative processes might be a key feature of the pathomechanism of Alzheimer's disease. Aberrations in the reparative neuronal response are likely to result from alterations of intracellular signal transduction cascades. As a consequence of abnormal intracellular signalling, the activation of those molecular events might be triggered in neurones which, in dividing cells, would lead to cellular transformation. In the present study, changes in the expression of the cyclin-dependent kinase inhibitor p16, a regulator of the orderly progression through the cell cycle, were investigated by immunocytochemical methods in the temporal cortex of patients with Alzheimer's disease. Both neurofibrillary tangles and neuritic components of plaques showed strong p16 immunoreactivity. These findings support the hypothesis that an aborted attempt of terminally differentiated neurones to re-enter the cell cycle might be a critical event in the pathology of Alzheimer's disease.