Intraindividual variation is smaller than the interindividual variation in serum TSH, free T(4), and free T(3) concentrations. This suggests that each individual may have a genetically determined thyroid function set-point. A representative sample of self-reported healthy twin pairs was identified through the Danish Twin Registry. A total of 284 monozygotic (MZ), 286 dizygotic same-sex (DZ), and 120 opposite-sex (OS) twin pairs were investigated. A classical twin study was performed. After adjustment for age, sex, and other covariates, the intraclass correlations of serum TSH, free T(4), and free T(3) were calculated. To elucidate the relative importance of hereditary and environmental factors on the variation of these hormone levels, quantitative genetic modeling was used. The intraclass correlations were consistently higher for MZ twin pairs than for DZ twin pairs. Regression analysis suggested that iodine intake played a small but significant role for the concentration of serum TSH and free T(4), whereas cigarette smoking was without influence. In quantitative genetic modeling, the heritability (with 95% confidence intervals) accounted for 64% (57-70%) of the variation in serum TSH concentration and 65% (58-71%) and 64% (57-70%), for the concentrations of free T(4) and free T(3), respectively. Genetic factors play a substantial role in controlling the pituitary-thyroid axis, indicating that each individual has a genetically determined thyroid function set-point. Whether this is of importance when treating individuals in whom pituitary-thyroid function has been disrupted by, e.g. hypo- or hyperthyroidism, remains to be clarified.