The chronic use of methadone or heroin results in various abnormalities in the transport and peripheral metabolism of thyroxine (T4). An increase in the thyroxine-binding capacity of the thyroxine-binding globulin and in the serum concentrations of T4 and triiodothyronine (T3) may be found in methadone and heroin addicts. In the heroin addicts these changes are accompanied by a decrease in the fractional turnover rate of T4; in patients receiving methadone the turnover rate is normal. Despite these abnormalities, serum free T4 concentrations and total T4 degradation rates were within the normal range of values, and the patients were clinically euthyroid. The causes of these changes remain obscure, probably because of the multiple effects these drugs have on various physiological processes.