THE body responds to stress by activation of the hypothalamic–pituitary–adrenal (HPA) axis and release of glucocorticoids. Glucocorticoid production in the adult regulates carbohydrate and amino-acid metabolism, maintains blood pressure, and restrains the inflammatory response¹. In the fetus, exogenous glucocorticoids accelerate maturation of lung² and gastrointestinal enzyme systems³ and promote hepatic glycogen deposition⁴. Corticotropin releasing hormone (CRH), a 41-amino-acid neuropeptide produced in the paraventricular nucleus of the hypothalamus and many regions of the cerebral cortex^{5, 6}, has been implicated in both the HPA axis⁷ and behavioural responses⁸ to stress. To define the importance of CRH in the response of the HPA axis to stress and fetal development, we have constructed a mammalian model of CRH deficiency by targeted mutation in embryonic stem (ES) cells⁹. We report here that corticotropin-releasing hormone-deficient mice reveal a fetal glucocorticoid requirement for lung maturation. Postnatally, despite marked glucocorticoid deficiency, these mice exhibit normal growth, fertility and longevity, suggesting that the major role of glucocorticoid is during fetal rather than postnatal life.