Because inflammation influences thyroid function, it was hypothesized that low plasma free triiodothyronine (fT3) in ESRD may be an unsuspected expression of the inflammatory state of these patients. This study investigated (1) the steady-state relationship between fT3 and inflammation markers (IL-6 and C-reactive protein) and markers of endothelial activation (intercellular adhesion molecule-1 [ICAM-1] and vascular cellular adhesion molecule-1 [VCAM-1]) in 200 hemodialysis (HD) patients and (2) the effect of intercurrent acute inflammatory/infectious processes on plasma fT3 in a group of 17 patients with chronic kidney disease (CKD). HD patients displayed lower (P < 0.001) plasma fT3 than healthy subjects (n = 31) and clinically euthyroid patients with chronic diseases and normal renal function (n = 262). When HD patients were subdivided into IL-6 tertiles, fT3 was progressively lower across tertile increments (P < 0.001). Accordingly, regression analysis showed strong and inverse associations (P < or = 0.002) between fT3 and IL-6, C-reactive protein, ICAM-1, and VCAM-1, and, with the exception of the ICAM-fT3 relationship, these associations remained highly significant (P < or = 0.004) in multiple regression analyses adjusting for demographic variables, risk factors, and other potential confounders. In patients who had CKD and were studied during intercurrent inflammatory/infectious processes, fT3 was significantly lower (P = 0.008) at the zenith of inflammation than after its resolution. Low circulating fT3 is frequently observed in inflammatory illnesses, and the same association exists in patients with CKD and in ESRD. This association may entail a causal link because fT3 is acutely and reversibly suppressed in patients with CKD during inflammatory processes triggered by intercurrent infections.