In addition to the well known structural stigmata which accompany the senile dementia of Alzheimer, attention is called to the presence of a group of robust changes which affect the fine vessels (capillaries, capillary arterioles and capillary venules), particularly of the cerebral cortex. These alterations include irregular pouches and excrescences on the vessels (a "lumpy-bumby" appearance), general thickening of the basement membrane, loss of the fine perivascular neuronal plexus which seems to invest each vessel, no matter how small, and the appearance of pits or lacunae in the vessel walls of about one half of the Alzheimer patients studied. None of these changes have been seen in a group of approximately age-matched, non-demented controls. Much of this perivascular neural plexus originates within a few specific subcortical fields, especially the locus ceruleus and the nucleus basalis of Meynert and basal forebrain area. These also happen to be included among those brain areas which experience the most marked neuronal atrophy or loss in Alzheimer's disease. Since there is some evidence suggesting that surgically induced vascular denervation in myocardium produces dramatic changes in vascular wall structure we wonder whether neuronal pathology developing initially in these subcortical areas may not play a significant role in the development of the characteristic neuropathology in Alzheimer's disease. These speculations emphasize the possible importance of a failing blood brain barrier in the development of the disease.