An understanding of the mechanisms of transport of circulating nutrients and hormones through the brain capillary wall, i. e., the blood-brain barrier, is important because the availability in brain of these substances influences a number of cerebral metabolic pathways. For example, the utilization by brain of glucose, ketone bodies and branched chain amino acids or the production of monoamines, acetylcholine, carnosine, and nucleosides may under certain conditions be influenced by BBB transport of circulating precursor nutrients. Steroid and thyroid hormones readily traverse the BBB via lipid-mediation and carrier-mediation, respectively. Although the steroid and thyroid hormones are tightly bound by plasma proteins, protein-bound hormone, not the free (dialyzable) moiety, is the major plasma fraction transported through the BBB. With regard to circulating peptides, the available evidence indicates peptides rapidly distribute into brain interstitial space of the circumventricular organs of brain, i. e., about six small regions around the ventricles which lack a BBB. Conversely, the absence of peptide carriers in the BBB prevents the rapid distribution of peptides into the vast majority of brain interstitial or synaptic spaces. However, recent studies indicate that some peptides, e. g., insulin, may bind specific receptors on the blood side of the BBB and thereby transmit messages to cells on the brain side of the BBB, without the peptide traversing the capillary wall.