I. Introduction PRETERM labor and prematurity with immaturity remain major problems in clinical obstetric practice. In North America approximately 5–8% of all deliveries occur preterm, and the figure may be higher in lower socioeconomic groups (1, 2). It is now clear that parturition results from a complex interplay of maternal and fetal factors, and in animals such as sheep birth results from the sequential maturation of an endocrine organ communication system. The fetal hypothalamo-pituitary-adrenal (HPA) axis occupies a pivotal position in this system. Cortisol from the fetal adrenal gland provides the trigger to the subsequent evolution of maternal endocrine changes, including enhanced prostaglandin F2α output, that result in increased uterine activity and birth. Fetal adrenal cortisol also participates in the stimulus to synchronous maturation of various fetal organ systems, including the lung, that are essential for extrauterine survival. Hence, this review will concentrate on discussing those factors that determine the ontogeny and activation of the ovine fetal HPA axis.