Dietary antithyrotoxic substances such as liver residue and hemoglobin (Hb) partially inhibited the absorption and enterohepatic recycling of oral or ip injected thyro-xine (T4). Approximately twice as much thyroxine was excreted into the feces and only half as much T4 was absorbed into the plasma when a single dose of I131-T4 was given to rats receiving a diet containing one of the antithyrotoxic substances. The poor T4 absorption was probably the result of at least 2 contributory factors. First, antithyrotoxic substances caused an oral dose of T4 to move rapidly through the lower ileum and large intestine, which are the most active sites for T4 absorption. The fecal mass was much greater in these animals, and this may have been responsible for the greater intestinal motility. Second, T4 probably formed an unavailable complex with the antithyrotoxic substance or its degradation product. Two types of evidence were obtained to support this concept the fecal T4 from Hb-fed animals had little biological activity; known antithyrotoxic substances inhibited the uptake of T4 by the mucosa of intestinal sacs made from the ileum. The thyroid glands of animals fed antithyrotoxic substances were more active (judged by increased thyroid I131 uptake values and histological examination), but the metabolic rates were the same as those of the controls. The probable explanation is that the thyroid had to work harder in the presence of antithyrotoxic factor to compensate for the greater fecal T4 excretion rate.