A panel of 14 lectins was used to investigate the expression of saccharides by cerebral microvessels (MBV) in ageing, Alzheimer's disease (AD) and Down's syndrome (DS). Broad increases in lectin binding with age may reflect changes in amount and diversity of glycoproteins due to the thickening of the basement membrane (BM) common in older persons. In AD, and in persons over 50 years of age with DS, binding of e-PHA, I-PHA and PAA was increased beyond that of age alone, as was that of UEA-I and BSA-1B4 in AD, but not in DS. Persons under 50 years of age with DS showed no changes inappropriate to their age. These specific increases in AD and DS may reflect selective disease-related changes in BM and could indicate an impaired blood-brain barrier (bbb) function or integrity. However, because they occur (in DS) after the deposition of amyloid (A4) protein and onset of neurofibrillary degeneration, it is unlikely they induce plaque and tangle formation. Such changes in MBV could stem from the loss of neurones from locus caeruleus, raphe and nucleus basalis (which are thought to innervate MBV and exert control over blood flow and permeability) that occurs in DS after 50 years of age.