A six-compartment model is proposed for the study of early iodine kinetics (150 min) in the human thyroid gland including three compartments for extrathyroidal spaces. The results were compared with those obtained with an open two-compartment thyroid model. In six euthyroid subjects the values of the unidirectional thyroid clearance R41 = 86 +- 25 ml/min and of the irreversible clearance R65 = 22 +- 9 ml/min were consistent with those generally accepted. With TSH stimulation a clear increase in the thyroidal pump effectiveness was found without an increase in the irreversible clearance. In four untreated thyrotoxic patients a tenfold increase in the unidirectional thyroid clearance was found (p less than 0.01). The binding rate was much less increased and overlapped with the normal values; a large increase in the iodide compartment volumes was found. The unidirectional clearance remained elevated in seven patients after Carbimazole treatment and the binding rates were reduced. The six-compartment model demonstrated a rapid exit from the bound iodine compartment. In three of four goitrous patients studied, the thyroid unidirectional clearance was significantly increased ( p less than 0.001). The volumes of the iodide compartments were much higher than those observed in the other groups. The method was applied to analyse the kinetics of the different parts of the thyroid.