A family with hereditary high serum thyroxine-binding globulin was studied. All the subjects studied were clinically euthyroid without goiter. The propositus (female), her mother and sister had high TBG, total T4 and total T3 with normal free T4, free T3 and TSH. Her father's thyroid function was within the normal range. Possible etiologic factors causing secondary hyper-TBG-nemia were ruled out in all the affected subjects. Isoelectric focusing demonstrated qualitatively normal microheterogeneity, ruling out possible TBG variations caused by liver diseases, estrogen therapy or pregnancy. Although the mechanism involved in the TBG increase awaits further investigation, it could be an abnormality in the gene controlling the synthesis of TBG.