The penetration of substances relative to freely-diffusible antipyrine was determined in regions of the maturing chick brain. Two amino acids were studied: tyrosine, which is essential to the brain and is a neurotransmitter precursor, and proline, a non-essential amino acid. During maturation the barrier toward proline developed to a much greater extent than that toward tyrosine. The penetrance of d-glucose, the main energy source for the brain, increased during maturation, while the penetrance of l-glucose, a metabolically inert stereoisomer of d-glucose, decreased. The results suggest differing rates of development of the blood-brain barrier to various substances. © 1976.