SUMMARYComplete turnover studies of thyroxine (T4), 3,5,3′‐triiodothyronine (T3), 3,3′,5′‐triiodothyronine (rT3), 3,3′‐diiodothyronine (3,3′‐T2), 3′,5′‐diiodothyronine (3′,5′‐T2) and 3′‐monoiodothyronine (3′‐T1) were performed in each of eight healthy subjects, eight hyperthyroid and eight hypothyroid patients, using the single injection, non‐compartmental approach. The median metabolic clearance rate (litre per day per 70 kg) in controls was, T4 1·19; T3 19·7. rT3 147; 3,3′‐T2 1073; 3′,5′‐T2 256 and 3′‐T1 518. Hyperthyroid patients had increased and hypothyroid patients reduced values. The median production rate (PR) (nmol per day per 70 kg) in controls was, T4 117, T3 39, rT3 52, 3,3′‐T2 35, 3′,5′‐T2 14 and 3′‐T1 27. The PR of all iodothyronines studied was increased in hyperthyroidism, the increase in PR of T3 being the most pronounced. Hypothyroid patients had reduced PRs, a reduction which was relatively less pronounced for T3. Assuming thyroidal secretion contributes little rT3 and 3′,5′‐T2, the conversion rates (CRs) of T4 to rT3 and further to 3′,5′‐T2 were calculated. CR of T4 to rT3 in controls was in median 34%. By comparison the CR in hyperthyroid patients was increased to 56% (P<0·05). In contrast the CR of rT3 to 3′,5′‐T2 was similar in controls and hyperthyroid patients, 26% v. 31%.Our data demonstrate, that quantitatively important amounts of 3,3′‐T2, 3′,5′‐T2 and 3′‐T1 are produced in man, and that deiodination of T4, the T3s and the T2s is a major metabolic pathway both in eu‐, hyper‐ and hypothyroidism. The daily production of all six iodothyronines studied is influenced by hyper‐ and by hypothyroidism. The activity of the 5‐deiodination of T4 seems to be enhanced during hyperthyroidism, possibly tending to counteract the hypermetabolic state. In contrast the 5‐deiodin