Sodium salt of dextran sulfate ester (MDS-Kowa, Kowa Co., Japan) was administered intravenously to 4 euthyroid subjects, 7 patients with hyperthyroidism and 5 patients with hypothyroidism. Serum FFA rose to the level 4-6 times higher than the preinjection level 15 min after the intravenous injection. At the same time, elutable fraction (EF) of T4, free T4, and binding capacity and concentration of TBPA increased, while binding capaty of TBG decreased. Addi tion of dextran sulfate to serum in vitro caused no change in binding capacity of TBG and EF of T,,. Addition of palmitic acid to serum in vitro with increas ing concentration resulted in a gradual decrease in the distribution of 131I-T4 to TBG and binding capacity of TBG, while EF of T4 gradually increased. Intravenous injection of dextran sulfate ester following the prior injection of protamine sulfate in dog caused a mild rise in serum FFA, but failed to increase the EF of T4. When reverse-flow paper electrophoresis was carried out after addition of 14C-palmitic acid to sera of normal and TBG-deficient subjects, it was confirmed that palmitic acid bound to albumin and TBG fraction.These results suggest that dextran sulfate ester raises serum FFA first, then the increased FFA combines with TBP at least with TBG, thus competing for binding sites with T4, and released T4 in turn increases free T4 level in the serum.heparinoid; free thyroxine; thyroxine-binding globulin Hollander et al. (1967) first reported that free fatty acids (FFA) and serum per cent free thyroxine (T4) increased by the intravenous injection of heparin. Braverman et al. (1969), on the other hand, reported that fluctuation of the con centration of FFA within the physiological range has little effect on free T4 in serum. The competition of FFA with T4 for one or other of T ,-binding globulin. (TBG), T4-binding prealbumin (TBPA) and albumin was supposed to be the cause of increase of free T4 through the rise of FFA.In the present report, sodium salt of dextran sulfate ester, a heparinoid which has intense lipemia-clearing activity,, was used to study the effect of FFA upon T4-binding protein (TBP) and free T4.