A level of thyroid hormone (TH) in agreement with the tissue requirements is essential for vertebrate embryogenesis and fetal maturation. In this study, we evaluate the immediate and long-term effects of incongruent intrauterine TH levels between mother and fetus using the TR^-/- knock out mouse as a model. We took advantage of the fact that the TR^-/- females have elevated serum TH but are not thyrotoxic due to resistance to TH (RTH). We used crosses between heterozygotes with wild-type phenotype (TR^+/-) males and TR^-/- females, with a hyperiodothyroninemic (high T₄ and T₃ levels) intrauterine environment (TH congruent with the TR^-/- fetus and excessive for the TR^+/- fetus), and reciprocal crosses between TR^-/- males and TR^+/- females, providing a euiodothyroninemic intrauterine environment. We found that TR^-/- dams had reduced litter sizes and pups with lower birth weight but preserved Mendelian TR^-/- to TR^+/- ratio at birth indicating that the incongruous TH levels did not decrease intrauterine survival of a specific genotype. The results of studies in newborns demonstrate that TR^+/- pups born to TR^-/- dams have persistent suppression of serum TSH without a peak. On the other hand, TR^-/- pups born to TR^+/- dams have lower serum TSH at birth and a tendency to peak higher, compared to TR^-/- pups born to TR^-/- dams. The studies in the adult progeny demonstrate that TR^+/- mice born to TR^-/- dams, and thus exposed to higher intrauterine TH levels, have greater resistance to TH at the level of the pituitary when stimulated with TRH. On the other hand, TR^-/- mice born to TR^+/- dams, and thus deprived of TH in uterine life, were more sensitive to TH when similarly stimulated with TRH. Thus, TH exposure in utero has an effect on the regulatory set-point of the hypothalamus-pituitary-thyroid axis which can be seen early in life and which persists into adulthood.