Studies in arginine vasopressin (AVP)-deficient Brattleboro rats suggest that AVP is the predominant secretagogue during the perinatal period. Here we tested the hypothesis that congenital lack of vasopressin differentially modifies the stress reactivity of male and female rat pups. Vasopressin- producing (heterozygous, AVP+) and AVP-deficient (AVP-) Brattleboro rat pups of both genders were used. In 10-day-old pups, 24-h maternal separation and single, as well as repeated, ether inhalation induced remarkable adrenocorticotropin (ACTH) elevation only in AVP+ pups, supporting the role of vasopressin in hypothalamo-pituitary-adrenal (HPA) axis regulation. Surprisingly, the corticosterone elevations were even more pronounced in AVP- pups, suggesting the possibility of an ACTH-independent corticosterone-secretion regulation. In the case of maternal separation, both the plasma ACTH and corticosterone levels were higher in females than in males, while in case of ether inhalation only the ACTH levels were higher in females. Gender did not influence the stress reactivity or the effect of the genotype. We conclude that the gender of the pups did not profoundly influence HPA axis activity (the mechanism seems to be the same), but in contrast to the general view, we suggest that the females have a more active HPA axis than the males already during the neonatal period. However, the resting corticosterone elevation - well known in adult females - is missing.