The potent synthetic glucocorticoid betamethasone 17,21-dipropionate (BMDP) produces adrenal hypertrophy in the rat foetus at late pregnancy by mediation of the hypothalamo-pituitary system, but causes adrenal atrophy, and acts as a normal glucocorticoid, in the adult rat. The change of the adrenal cortical response to the BMDP treatment was investigated in perinatal rat offspring. The pituitary ACTH potency was also determined in rat foetus treated with BMDP. The time course of the adrenal corticosterone level after the BMDP treatment was similar to that of the plasma level on day 19 to 21 in the rat foetus from the adrenalectomized mother, both decreased at 2 h, but rose gradually at 4 h to 6 h, exceeding the control level at 24 h and 48 h after the BMDP treatment. The pituitary ACTH potency in the foetus decreased at 24 h and 48 h after the BMDP treatment, suggesting that ACTH released from the foetal pituitary stimulated adrenal corticoidogenesis. Maternal adrenalectomy did not essentially alter this stimulating activity of BMDP, which appeared in the perinatal rat offspring, only when BMDP was administered during the foetal period. These findings suggest that the hypothalamo-pituitary adrenocortical response to the treatment with BMDP drastically changes at the early neonatal age.