In several studies lactation has been shown to be associated with a hypothalamic-pituitary-adrenal axis hyporesponsiveness to physical and psychological stressors. As it is not known whether the marked blunting of endocrine stress reactivity in women can be ascribed to suckling as a short-term effect or to lactation in general, the acute effects of suckling on the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal-medullary system responses to mental stress were investigated in lactating women.Forty-three lactating women were randomly assigned either to breast-feed or to hold their infants for a 15-min period with the onset 30 min before they were exposed to a brief psychosocial stressor (Trier Social Stress Test). Both breastfeeding and holding the infant yielded significant decreases in ACTH, total plasma cortisol, and salivary free cortisol (all P < 0.01). There were no significant differences in baseline hormone levels between the groups 1 min before the stress test. In response to stress exposure, ACTH, total plasma cortisol, salivary free cortisol, norepinephrine, and epinephrine were significantly increased in all lactating women (all P < 0.001). However, total cortisol and free cortisol responses to stress were attenuated in breast-feeding women (P ؍ 0.001 and P ؍ 0.067, respectively), who also showed significantly decreasing PRL levels during the stress test (P ؍ 0.005). In addition, there was no change in plasma oxytocin or vasopressin in response to the stressor. Breast-feeding as well as holding led to decreased anxiety (P < 0.05), whereas, in contrast, stress exposure worsened mood, calmness, and anxiety in the total group (all P < 0.001).From these data we conclude that lactation in women, in contrast to that in rats, does not result in a general restraint of the hypothalamic-pituitary-adrenal axis response to a psychosocial stressor. Rather, suckling is suggested to exert a short-term suppression of the cortisol response to mental stress. (J Clin Endocrinol Metab 86: 4798 -4804, 2001) E VIDENCE FROM ANIMAL and human studies has suggested that suckling is associated with significant alterations in the reactivity of the hypothalamic-pituitaryadrenal (HPA) axis during the postpartum period (1, 2). Observations in the lactating rat have shown an endocrine hyporesponsiveness to physical and psychological stressors, including attenuated secretion of ACTH (3-7), corticosterone (3-5, 8 -11), catecholamines (12), oxytocin (9, 13-15), and PRL (12, 16).In humans, the effect of lactation on stress-responsive neurohormonal systems has been explored, to date, only for treadmill exercise. Altemus and associates (17) found significantly attenuated plasma ACTH, cortisol, and glucose responses to physical stress in lactating compared with nonlactating women. However, the effects of suckling on endocrine as well as behavioral responses to a psychosocial stress paradigm in humans have not yet been investigated. More important, it is not known whether the marked blunting of endocrine stress responsi...