Context: The interindividual variability in thyroid hormone function parameters is much larger than the intraindividual variability, suggesting an individual set point for these parameters. There is evidence to suggest that environmental factors are more important than genetic factors in the determination of this individual set point. Objective: This study aimed to quantify the effect of genetic factors and (fetal) environment on the early postnatal blood T<inf>4</inf> concentration. Methods: This was a classical twin study comparing the resemblance of neonatal screening blood T<inf>4</inf> concentrations in 1264 mono- and 2566 dizygotic twin pairs retrieved from the populationbased Netherlands Twin Register. Maximum-likelihood estimates of variance explained by genetic and environmental influences were obtained by structural equation modeling in data from fullterm and preterm twin pairs. Results: In full-term infants, genetic factors explained 40%/31% of the variance in standardized T<inf>4</inf> scores in boys/girls, and shared environment, 27%/22%. The remaining variance of 33%/47% was due to environmental factors not shared by twins. For preterm infants, genetic factors explained 34%/0% of the variance in boys/girls, shared environment 31%/57%, and unique environment 35%/43%. In very preterm twins, no significant contribution of genetic factors was observed. Conclusion: Environment explains a large proportion of the resemblance of the postnatal blood T<inf>4</inf> concentration in twin pairs. Because we analyzed neonatal screening results, the fetal environment is the most likely candidate for these environmental influences. Genetic influences on the T<inf>4</inf> set point diminished with declining gestational age, especially in girls. This may be due to major environmental influences such as immaturity and nonthyroidal illness in very preterm infants.