Necturus maculosus, a neotenous urodele, apparently fails to respond to thyroactive compounds by undergoing metamorphosis. Experiments have been performed to determine whether or not other manifestations of thyroid hormone action could be induced in this species. Following administration to the Necturus of thyroxine, 3:5:3′-L-triiodothyronine, tetraiodothyroacetic acid, triiodothyroacetic acid, mono- or diiodotyrosine, respiration was measured in tissue slice preparations, and the electrophoretic characteristics of the plasma proteins and the hemoglobin were determined. The effect of thyroxine added in vitro on the oxidation of succinate by homogenates of the Necturus ventricle also was studied. No evidence of thyroid hormone action could be obtained. A study of thyroid hormone metabolism in the Necturus was then carried out. In contrast with findings obtained in the tadpole, homogenates or slices of tissue from the Necturus completely failed to deiodinate thyroxine and its derivatives, although a system for deiodinating the iodotyrosines was present. Homogenates of the Necturus liver were capable of deaminating thyroxine. Attempts to initiate enzymic deiodination of thyroxine by the addition of certain metabolic cofactors, or by the prolonged administration of thyroxine, were unsuccessful. Thus, the Necturus appears to afford another instance in which a lack of response to thyroid hormones is accompanied by unusual properties with regard to hormonal metabolism.