To investigate the possible presence of thyroglobulin (Tg of different molecular sizes in plasma, blood specimens were drawn from patients during and after surgery for thyroid adenoma. Tg was measured in all serum samples by a radioimmunoassay. Selected samples were fractionated on a sepharose CL-6B column, and the fractions were assayed for Tg antigen. In serum drawn at maximum Tg concentration, molecular weights of Tg antigen ranging from 660,000 (19S) to less than 100,000 were found. 6 h later the Tg antigen of mol. wt. less than 100,000 could not be detected, and after 3 days only 19S Tg was present. Correspondingly the plasma Tg concentration vs. time curve showed a biphasic course from which two half-lives could be estimated. For 19S Tg, ta1/2 had a mean value of 4.3 days, whereas the over-all half-life for the mixture of smaller molecules, tb1/2, had a mean value of 3.7 h. The smaller molecules also showed different antigenic reactivity in the assay indicating an altered structure of the molecules. The assumption that this might be due to lack of sialic acid would explain the faster catabolic rate.