Opiate peptides administered on one side of the blood-brain barrier can exert powerful effects on processes occurring on the other side. There is evidence for direct passage of opiate peptides and their analogues across this barrier. Beta-Endorphin can enter the cerebrospinal fluid after systemic administration, but its entry into brain tissue has been more difficult to demonstrate, even though analogues enter at a modest rate. Enkephalins enter and exit the central nervous system as intact molecules by a combination of saturable and nonsaturable mechanisms. A family of transport systems may exist with varying affinities for the opiate enkephalins, antiopiates like tyrosine melanocyte-stimulating hormone inhibitory factor 1 (Tyr-MIF-1), and related peptides. The major system transporting these peptides, termed Peptide transport system 1, can be influenced by several factors with entry and exit rates affected by aging, drugs, amino acids, monoamines, aluminum, stress, and ethanol addiction and withdrawal. The homeostatic role of the blood-brain barrier thus extends to the regulation of the bidirectional transport of informational peptides such as the opiates.