Biologically active corticotrophin-releasing-hormone (CRH) is produced by the placenta in large amounts and can be measured in the maternal circulation during third trimester of pregnancy. Its physiological significance is unknown. To further investigate the action of CRH in pregnancy, we performed a standard CRH-test (1 micrograms/kg synthetic human CRH) in seven pregnant women 1 week prior to their calculated delivery data and 4-5 weeks post-partum. No response of plasma ACTH to CRH administration could be measured in any of the third trimester pregnant women. Post-partum, basal ACTH levels were significantly lower (1.6 +/- 0.3 vs 5.3 +/- 0.2 pmol/l) and reacted promptly to CRH administration (1.6 +/- 0.3-4.2 +/- 0.5 pmol/l; P less than 0.05). Concentration of cortisol in plasma and salivary cortisol paralleled the ACTH response to administration of CRH. However, one pregnant woman experienced physical and emotional stress during the CRH-test and reacted with a sharp rise in cortisol secretion. The lack of the ACTH and cortisol response in this study to exogenously administered CRH in third trimester pregnancy may be due to high circulating glucocorticoid concentrations, desensitization of the pituitary corticotroph and/or in part due to circulating specific CRH-carrier protein.