SERUM total and non-protein-bound (“free”) fraction of thyroxine and triiodothyronine together with the urinary unconjugated concentrations of these hormones have been measured in normal subjects and in a group of hospital in-patients suffering from a variety of moderately severe subacute or chronic non-thyroidal illness. Significantly higher concentrations of serum free thyroxine and even more striking increases in renal excretion of thyroxine were found in sick subjects. No such changes were apparent in the case of triiodothyronine. It is suggested that these findings are best explained by the presence in sick individuals of circulating small molecular weight compounds which competitively inhibit thyroxine binding to serum proteins and its active reabsorption by renal tubules.