This study attempted to determine the placental release of corticotrophin-releasing hormone (CRH) into the umbilical circulation, and the factors which affect it, by measuring venous and arterial levels for CRH across the umbilical circulation in labouring as well as non-labouring elective caesarean section patients. The relationship with measures of fetal oxygenation and acid-base status at birth was investigated also. Forty-eight patients were studied (term labour n = 30, term elective caesarean section n = 12, and preterm labour n = 6) with blood sampling from a clamped segment of cord after delivery of the fetus and from the cord at its insertion into the placenta after delivery of the placenta, with subsequent measurement of blood gases, pH, base excess, and CRH. For all patients, mean plasma CRH levels in the umbilical and placental vein (115+/-13 and 145+/-18 pg/ml) were higher than those from the corresponding artery (85+/-7 and 102+/-8 pg/ml, P<0.01 and P<0.05, respectively), indicating placental release of CRH into the fetal compartment. In addition, placental venous and arterial cord CRH levels were higher than those from the corresponding umbilical levels (P<0.01 and P<0.02, respectively) indicating continued placental release of CRH into blood within the placenta after clamping of the umbilical circulation and delivery of the fetus. While plasma CRH levels from respective cord vessels were all significantly higher in labouring patients at term versus elective caesarean section patients, there were no differences compared with preterm labouring patients. For all patients, CRH as measured in both the umbilical and placental vein showed a modest inverse correlation to base excess as measured in the umbilical artery, -0.31 and -0.33, respectively, both P<0.05. It is concluded that CRH is released by the placenta into the fetal compartment and is increased with both term and preterm labour, and with metabolic acidosis during labour, supporting a role in the endocrine events of labour and/or compensatory changes in uteroplacental blood flow.