In view of the reported enhanced sensitivity to iodide-induced hypothyroidism in patients with cystic fibrosis, studies were carried out to determine the possible mechanism of this abnormality. The intrathyroid organification of iodide, as assessed by the iodide-perchlorate discharge test, was normal in patients with cystic fibrosis, strongly suggesting that an organification defect was not present. The serum TSH response to TRH was not significantly different from the response in normal children and adolescents. Serum T4 concentration was normal whereas that of T3 was decreased in patients with cystic fibrosis, strongly suggesting decreased peripheral conversion of T4 to T3, as commonly occurs in nonthyroid illness. Our findings do not delineate the mechanism whereby patients with cystic fibrosis develop iodide-induced hypothyroidism.