An electron beam x-ray microanalysis method was developed to examine the cellular and regional distribution of metals in unfixed, unstained, fresh frozen human brain tissue. Analysis of samples from patients with Alzheimer's disease demonstrated that neither aluminum calcium or silicon is accumulated significantly in senile plaques as compared to surrounding brain tissue or brain tissue from aged-matched controls. Rates of entry of selected metals into the central nervous system were determined in awake, unanesthetized rats following intravenous administration. Values were found to differ among metals by at least two-orders of magnitude with lead > calcium - cadmium > gallium for uptake into brain. Calcium influx into cerebrospinal fluid is maintained constant during chronic hypocalcemia by a saturable vitamin D-independent transport mechanism at the choroid plexus epithelium. Low dietary calcium was shown to facilitate manganese uptake and deposition in brain. Essential nutrients that are required for brain metabolism are transported into brain from plasma by specific, saturable transport mechanisms at the bloodbrain barrier. A brain perfusion technique was used to characterize the transport systems for glucose and amino acids and to evaluate the structural specificity of the neutral amino acid transport system. The availability of albumin-bound tryptophan for uptake into brain was found to be dependent on the cerebral perfusion rate. The rate of transport of neutral amino acids into brain was found to decrease during development and then remain constant with age in the rat. The pattern of amino acid transport matched that of brain Protein synthesis, suggesting that blood-brain barrier transport capacity is modulated to meet the metabolic needs of the brain..