Blood plasma and cerebrospinal fluid (CSF) samples were collected from adult female rabbits (New Zealand White), newborn, and embryos at 18, 20, 24, and 28 days of gestation. Samples were analyzed for total protein using the Folin phenol reagent. During development, mean total protein of blood plasma rose sharply from 12.45 to 12.51 mg/ml at 18 to 20 days to 37.56 mg/ml at 28 days. Levels further increased to 54.06 mg/ml in the newborn and to 66.18 mg/ml in the adult. The protein concentration of cerebrospinal fluid was constant at 5.20 to 5.29 mg/ml between 18 and 20 days of gestation, but steadily decreased to 3.53 mg/ml at 28 days. By birth, the CSF protein concentration was further reduced to 2.08 mg/ml, and this level differed only slightly (P < 0.05) from CSF protein values determined for adults. These data indicate that the blood-cerebrospinal fluid barrier to proteins begins to function by 18 to 20 days of gestation, and the protein concentration of cerebrospinal fluid approaches the normal adult value soon after birth. © 1979.