The binding capacity of thyroxine-binding globulin (TBG), and total and dialysable thyroxine in the cerebrospinal fluid (CSF) and in serum have been estimated in 13 euthyroid patients with normal and elevated CSF protein and in 5 hyperthyroid and 5 hypothyroid patients. In the normal group, the mean value of TBG in CSF was found to be 2.7 ng/ml and 207 ng/ml in serum. TBG in CSF in relation to the total protein content was found to be much higher than TBG in the serum in relation to the total serum protein. In the euthyroid patients with elevated CSF protein TBG was also increased but not proportional to the increase in the protein concentration. In the hyperthyroid patients TBG in CSF was decreased and was lower than the elevated total thyroxine values. Dialysable thyroxine, however, showed only a moderate increase indicating that proteins other than TBG must bind a considerable part of total thyroxine in CSF in hyperthyroid patients. In myxoedema TBG was found to be elevated in proportion to the slightly elevated CSF protein content. It is concluded that TBG in normal CSF seems to be the physiologically most important thyroxine-binding protein.