In studying the solubility characteristics of thyroglobulin, it was found that the removal of sialic acid residues from either human or hog thyroglobulin by treatment with neuraminidase markedly decreased the solubility in salt solutions. On the other hand, naturally sialic acid-rich thyroglobulin obtained from human diffuse goiter was slightly more soluble than thyroglobulin in which sialic acid content was within the normal range. However, the desialized preparations prepared from both normal and sialic acid-rich thyroglobulin showed markedly lower solubility and further, showed no significant difference in solubility between them. These results indicate that the surface charge of thyroglobulin which influenced the salting-out property depends largely on the number of sialic acid residues in a thyroglobulin molecule, not on the degree of iodination of thyroglobulin.