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The functional maturation of the hypothalamic–pituitary–adrenal (HPA) axis has been studied in rats of 20–35 days of age made hypothyroid by the administration of thiouracil from conception. Basal concentrations of corticosterone in serum were normal in hypothyroid animals. Ether stress led to an increase in corticosterone content of the adrenal glands of hypothyroid and normal rats but not to a rise in serum corticosterone of hypothyroid rats until 30 days of age. Corticosterone secretion in response to ACTH administration was subnormal in hypothyroid rats. The hypothyroid state delays the development of the hypothalamic–pituitary–portion of the HPA axis until 30 days of age and causes a diminution in the adrenal response to ACTH beyond this time.