The secretion rates of thyroglobulin were measured under basal conditions and after exogenous and endogenous thyrotropin stimulation in 23 patients during surgery. In 11 patients with normal thyroid glands the median secretion rate of thyroglobulin was 0.7 pmol/24 h. Higher secretion rates were observed in 8 patients with nontoxic nodular goiter (median 22 pmol/24 h; p < 0.001) and in 4 patients with thyroid malignancy (median 2.2 pmol/24h; p < 0.05). Within 10 min after administration of highly purified human thyrotropin into the thyroid artery an increase of the secretion rates was observed in the 9 patients studied with normal thyroid glands and 5 patients with nontoxic nodular goiter. TRH administration to 5 patients induced a slight but nonsignificant increase of the secretion rate of thyroglobulin after 20 min. These results show that thyroglobulin is secreted directly into the thyroid venous blood. They also confirm that thyrotropin is an important regulator of the thyroglobulin secretion.