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 breast-feeding 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.