Serum levels of the protein S-100beta are dependent on three factors: rate of production, permeability of the blood-brain barrier, and rate of clearance. In the developing fetus and neonate all of these factors change at different rates. This study was performed to determine how serum S-100 levels varied during fetal and early postnatal life. Blood samples were obtained from 41 fetal and neonatal lambs. The blood was separated in a centrifuge and the serum drawn off and assayed for S-100beta using a commercially available radioimunoassay kit. S-100beta did not appear in the blood until halfway through pregnancy. Thereafter, levels steadily increased until 1 month after birth. Following this, S-100beta levels decreased progressively until by 1 year of age, they had reached a plateau. S-100beta levels change significantly with normal fetal and neonatal maturation. Valid interpretation of other data from subjects of similar developmental stage must take into consideration this physiological variation.