In 8-day-old rat newborns, the pituitary response to 2 min of ether inhalation was noted to vary according to sex. Plasma ACTH levels were similarly increased in males and females at the end of ether exposure; however, during the following 30 min, ACTH levels were always higher in females than in males. In order to verify that the putative masculinization of some neuroendocrine pathways involved in the pituitary response to ether stress was the result of the transitory surge of testosterone at birth, fetuses at term were delivered by cesarean section and thereafter immediately castrated or sham-castrated under cold anesthesia (males), injected with testosterone heptylate (1 mg s.c.) or olive oil used as solvent (females) before being put in the care of a nurse. The rise in plasma testosterone levels during the 1st h after birth was prevented or stopped in males put at 2 °C. At the 8th postnatal day, the newborns were subjected to 2 min of ether inhalation; they were sacrificed either just, before or after the end (0 and 30 min) of the stress procedure. Plasma immunoreactive ACTH level and adrenal corticosterone content were measured. The pituitary response, shown by the ACTH increase, in castrated or sham-castrated males and testosterone-injected females was similar to that of intact males but very different from that observed in olive-oil-injected or intact females. The rise in adrenal corticosterone content 30 min after ether inhalation was greater in intact and olive-oil-injected females than in testosterone-injected ones or in males; adrenal response was well correlated with the maintenance of ACTH release in the former and the decrease following transitory surge in the latter. Present data suggest – in the male, prenatal differentiation of the neuroendocrine pathways involved in the pattern of ACTH release in response to ether inhalation – in the female, the existence of androgen-sensitive structures in early postnatal