Aging is commonly associated with progressive deterioration in central nervous system (CNS) function. Nutritional factors or environmental toxins have important effects on CNS degenerative changes. The blood-brain barrier (BBB) is a major modulator of nutrient delivery to the CNS. The tight junctions and the paucity of pinocytosis or fenestrations in brain capillary endothelium act as an effective barrier between the CNS and the circulating toxic agents. Senescence is associated with significant, though often subtle, changes in BBB. Conditions which are commonly associated with aging, such as hypertension and cerebrovascular ischemia, aggravate the age-related alterations in BBB function. The histologic changes in brain vasculature with aging is region selective and species specific. The common age-related histologic changes include loss of capillary endothelial cells, elongation of the remaining endothelial cells, and decreased capillary diameter in rat cortex, but not in the monkey or human cortex, and a decrease in the number of mitochondria in endothelial cells of the brain capillaries in the monkey but not in the rat. The age-related alterations in BBB transport function include a decrease in BBB choline transport with aging and decreased brain glucose influx. The BBB neutral amino acid transport appears to be unaltered in the aged mice. Most of the studies reported so far have failed to show a significant age-related alteration in BBB permeability to water-soluble substances and high molecular weight solutes in the absence of neurological disease. A more profound change in BBB permeability appears to be associated with Alzheimer's disease. Immunohistological studies have demonstrated the presence of serum proteins in the cerebrovascular amyloid in patients with Alzheimer's disease.(ABSTRACT TRUNCATED AT 250 WORDS)