A highly specific and precise radioimmunoassay for thyroxine-binding globulin (TBG) has been developed. Crossreactivity with albumin and prealbumin was excluded. The normal range in young adults was 0.97 mg/100 ml. In childhood TBG was elevated (1.34 mg/100 ml) also in old age (1.28 mg/100 ml). In normals and in childhood there was a good correlation of TBG with thyroxine (T4). T4 did not correlate with TBG with regard to age. Triiodothyroxine (T3) did not correlate with TBG in any group. T4 and T3 exhibited a progressive decrease with age. No correlation between age and TBG was found. In mild thyrotoxicosis (T3 : 4.5 ng/ml, with normal T4 and negative TRH-test) TBG was slightly increased (1.20 mg/100 ml), whereas in more severe hyperthyroidism (T3 : 6.4 ng/ml, T4 : 16.3 mug/100 ml) TBG concentration was not significantly different from normals. In hypothyroidism TBG was elevated (1.26 mg/100 ml). The conclusion from these data is that TBG does not follow the progressive decrease of T4 and T3 with age. Thus, age-dependent euthyroid ranges for thyroid hormone concentration, including TBG concentration, must be established for better clinical discrimination of thyroid function. Possible dependence of TBG on the nature of thyroid hormone concentration must be considered in the production and peripheral kinetics of thyroid hormones.