Sedimentation constant and iodination level of TG have been studied in 16 human normal and goitrous thyroid glands. S values are significantly reduced in poorly iodinated glands (17.8 ± 0.4 S, range: 17.2 to 18.6). The S values remain normal (19 ± 0.1 S) for a broad range of iodination levels and is only reduced below a critical iodination level which is situated at 0.1%. Results support the hypothesis that the metabolic abnormalities in non-toxic goitre are related to a modification of the spatial configuration of the thyroglobulin molecule and occur at a critical level of iodination of this protein. 1 Work carried out with the assistance of a grant from the National Fund of Scientific Research, under the ULB - PISA Euratom Contract, No 20.060.