Iodine metabolism has been studied in 20 patients with advanced chronic renal insufficiency due to primary renal disease, and thyroxine turnover in another 5 similar patients. Comparatively to 18 controls, the uremic patients had a lower urinary iodine excretion, and a much lower renal iodide clearance, which, however, was not as much decreased as the creatinine clearance. The normal relation between the renal iodide and creatinine clearances was disturbed when the latter was 6.3 ml/min or lower, and in these cases the renal iodide clearance exceeded the corresponding creatinine value. The plasma inorganic iodine (PII) was increased because of the iodide retention to (mean ± SE) 0.84 ± 0.17 µg/100 ml, compared to 0.12 ± 0.01 in the controls. The thyroidal iodide clearance (Th. Cl.) rate was decreased (22.8 ± 4.44 ml/min vs. 36.7 ± 6.48), but in spite of this decrease, the absolute iodine uptake (AIU) by the thyroid, which is calculated as AIU = Th. Cl. X PII, was increased (7.1 ± 1.37 vs. 1.9 ± 0.30 µg/h). The serum protein-bound iodine was normal. The PII, Th. Cl. and AIU values and the relation among them in renal insufficiency were comparable to those observed after chronic administration of small amounts of iodine. The radiothyroxine studies suggested an increased space of distribution and so, despite a decreased fractional turnover rate, an increased metabolic clearance and degradation rate.