Recent studies in humans suggest that alterations in the activity of the neuroendocrine system mediate the effects of psychosocial stress on fetal development and birth outcome. Chronic maternal distress compromises the normal regulation of hormonal activity during pregnancy and elevates free circulating corticotrophin-releasing hormone (CRH), probably of placental origin, before the normal increase occurs at term. Excess CRH, and other hormones like cortisol and met-enkephalin that pass through the placenta, could precipitate preterm labor, reduce birth weight and slow growth rate in prenatally stressed infants. CRH and/or cortisol have also been associated with impaired fetal habituation to stimuli and temperamental difficulties in infants. These changes may result from actions of the hormones on their receptors in the fetal limbic system. In the rat, gestational stress and excess maternal and fetal plasma corticosterone cause downregulation of fetal glucocorticoid (GR) and mineralocorticoid (MR) receptors and impair the feedback regulation of the hypothalamic-pituitary adrenal (HPA) axis in infancy and adulthood. The impairment in HPA axis activity can be prevented by maternal adrenalectomy and mimicked by administration of glucocorticoids. Gestational stress also increases CRH activity in the amygdala and the incidence of anxiogenic and depressive-like behavior in rats and non-human primates, which can be ameliorated by CRH antagonists. Excess amounts of CRH and cortisol reaching the human fetal brain during periods of chronic maternal stress could alter personality and predispose to attention deficits and depressive illness through changes in neurotransmitter activity.