To assess the role of maternal glucocorticoid milieu on the hypothalamic-pituitary-thyroid (HPT) function of the offspring, we adrenalectomized (ADX) pregnant dams on gestation day 8, and implanted a placebo pellet or a continuous release 50 mg or 75 mg corticosterone (CORT) pellet. Maternal ADX led to realignment of the balance between maternal and fetal plasma CORT levels resulting in an increase in CORT of fetal origin in the maternal compartment. Maternal ADX and low levels of CORT replacement had no discernable effect on maternal pituitary-thyroid measures. In contrast, the increase in fetal CORT, as a consequence of the absence of maternal glucocorticoids, decreased birth weight in neonates, decreased adult hypothalamic TSH-releasing hormone (TRH) mRNA levels and increased plasma TSH levels in both male and female adult offspring; all of which were reversed by administration of basal levels of CORT to the pregnant ADX dam. Decreased plasma T3 concentrations in female offspring were reversed by administration of the higher levels of CORT to the ADX dams. Our data indicate that maternal glucocorticoids modulate the developing HPT axis.