At moderate iodination levels (20 iodine at atoms/molecule), human thyroglobulin (hTgb) produces after reduction a thyroxinyl-peptide of 26 kDa which represents the N-terminal part of the protein. At higher iodination levels, the 26-kDa peptide is accompanied by another T4-containing peptide of 18 kDa. A precursor-product relationship between the 26- and 18-kDa fragments was demonstrated by the study of the tryptic fragments of both hormonopeptides. In addition, comparison with the protein sequence deduced from the nucleotide sequence of the 5'-end of hTgb mRNA demonstrated that the N-terminal region of Htgb from which are issued the 26-kDa peptide and its 18-kDa derivative is especially sensitive to proteolysis. This character is possibly related with a facilitated release of thyroid hormones in vivo.