The effects of peptides on brain function suggest therapeutic and pathologic roles for these substances. Many peptides cross the blood-brain barrier (BBB) by transmembrane diffusion as a function of their lipid solubilities. Other peptides, such as the enkephalins, Tyr-MIF-1, vasopressin-related peptides, and peptide T-like peptides, are transported by carrier-mediated systems. Passage is influenced by aging, stress, lighting, drugs, amino acids, and neurotoxins. Disruption of the BBB results in complex changes in the blood and CSF levels of peptides. Peptides influence the passage of glucose, amino acids, and inorganic acids and may affect the integrity of the BBB. Peptide-BBB interactions have been suggested to play direct roles in dialysis dementia and maple syrup urine disease; they may be expected to be involved in other disorders of the CNS.