Objective: Prolonged critically ill patients have low circulating thyroid hormone (TH) levels Without a rise in TSH. it condition labeled 'the low tri-iodothyronine (T-3) syndrome'. Currently, it is not clear whether this represents all adaptive response. We examined the role of TH transporters monocarboxylate transporter 8 (MCT8, also known its SLC16A2) and MCT10 in the pathogenesis of the low T-3 syndrome in prolonged critical illness. Methods: A clinical observational study in critically ill patients and all intervention study in all ill vivo animal model of critical illness. Gene expression levels of MCT8 and MCT10 were measured by real-time PCR. Results: In prolonged critically ill patients. we measured increased MM'S but not MCT10 gene expression levels in liver and skeletal muscle as compared with patients undergoing acute Surgical stress. In it rabbit model of prolonged critical illness, gene expression levels of MCT8 ill liver and of MM 0 in skeletal muscle were increased as compared with healthy controls. Treatment of prolonged critically ill rabbits with TH (thyroxine + T-3) resulted in a downregulation or gene expression levels of MCT8 ill liver and of MCT10 ill muscle. Transporter expression levels correlated inversely with circulating TH parameters. Conclusions: These data Suggest that alterations in the expression of TH transporters do not play a major role in the pathogenesis of the 'low T-3 syndrome' but: rather reflect a compensatory effort ill response to hypothyroidism.