We are increasingly exposed to environmental and occupational hazardous chemicals, which modulate hormonal activity and/or mutagenicity in mammals. In the present study, we investigated the effects of sex-steroid hormones on adrenocortical responsiveness to adrenocorticotropic hormone (ACTH) in neonatal rats. The levels of corticosterone increased with the dose of ACTH in adrenal cells of males and females in vitro. Although castration markedly augmented the responsiveness in male rats, testosterone-replacement in the castrated male rats inhibited the enhancement and, furthermore, the treatment with testosterone suppressed the responsiveness in 14-day-old intact female rats, too. Castration enhanced the level of ACTH receptor mRNA to 3-fold of that in intact male rats at 14 days of age, but replacement treatment with testosterone in castrated male rats lowered the elevated levels. These findings suggest that: 1) the hyporesponsiveness of adrenocorticosteroid in the stress hyporesponsive period of neonates might be dependent on the reduction of ACTH receptor mRNA, and 2) endocrine-disrupting chemicals, with characters of androgens, estrogens or gonadotropin-releasing hormones, might affect the responsiveness to ACTH and the ACTH receptor mRNA expression levels in adrenal cells of neonates.