The mechanism whereby euthyroidism appears to be maintained in patients with nonthyroidal disease (NTD) who have decreased plasma total and free triiodothyronine (T3) concentrations (low T3 syndrome) will be studied in patients with neoplastic diseases and in rats bearing the Walker 256 carcinoma in the thigh. Similarly to humans with NTD, tumor-bearing rats have a decrease in plasma T3 but their plasma thyrotropin (TSH) concentration is normal. In the rat, plasma thyroxine (T4) concentration is decreased as well. The observation that hepatic nuclear T3 receptor concentration is decreased in the tumor-bearing rat will be extended to an examination of receptor concentration in rat anterior pituitary and human lymphocytes. A decrease in lymphocyte T3 receptor concentration in patients with NTD and the low T3 syndrome will indicate that the tumor-bearing rat may be a useful model for studies of receptor regulation, nonhistone protein metabolism and biologic responses to T3 in NTD. The effect of neoplasms on biologic responses to thyroid hormones will be determined by measurement of the augmentation of plasma TSH concentration in response to a further decrease in plasma thyroid hormone, the release of TSH after administration of thyrotropin releasing hormone (TRH), and increase in thyroid hormone sensitive hepatic malic enzyme and alpha-glycerophsophate dehydrogenase activities.