The form and distribution of senile plaques (SP) and neurofibrillary tangles (NFT) has been examined in the brains of 13 patients with Down's syndrome (DS), aged less than or equal to 50 years, using immunocytochemical and silver staining procedures. SP become present within the brain before NFT and these appear firstly as fine, even, diffuse areas of anti-amyloid (A4) protein immunoreactivity in the absence of any discernable neuritic change. Later the amount of anti-A4 protein in SP increases and SP show a marked surrounding neuritic response which is detectable using either silver or anti-paired helical filament (PHF) staining methods. At this stage NFT also become detectable within the perikaryon of nerve cells in both the cortex and the subcortex, with the large stellate neurones of layer II of the entorhinal cortex showing an early involvement. By the age of 50 years, most patients are well on the way towards achieving (and some have already achieved) that pattern of SP and NFT morphology and distribution that is typically seen in patients over 50 years of age with DS and in other patients in the general population with Alzheimer's disease.