There are two biologically active thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Most T3 is produced extrathyroidally, so that alterations in circulating thyroid hormone concentrations may occur as a result of both thyroidal and extrathyroidal abnormalities. Extrathyroidal T4 conversion to T3 is decreased in patients with different acute and chronic illnesses. When T4 conversion to T3 is impaired and serum T3 concentrations decline, serum concentrations of biologically inactive 3,3',5'-triiodothyronine (reverse T3) increase. In this review, we present current information on thyroidal and extrathyroidal T4 and T3 production in normal subjects and patients with various thyroid diseases and other illnesses, consider the physiologic significance of these changes, and discuss the value and interpretation of various iodothyronine measurements.