Variations in the serum concentration of interleukin-6 (IL-6) have been reported concomitantly with thyroid dysfunction: increased serum IL-6 levels have been found in patients with thyroidal destructive processes, such as subacute thyroiditis, some forms of amiodarone-induced thyrotoxicosis, or after percutaneous ethanol injection into "hot" thyroid nodules, as a result of the cytokine release from the damaged thyrocyte. In addition, recent in vitro evidence suggests that IL-6 might account, at least in part, for changes of thyroid economy found in nonthyroidal illness (NTI). In this cross-sectional study we addressed this problem by measuring serum IL-6 levels in 71 patients with NTI, due to neoplasia (n = 25), chronic liver disease (n = 9), chronic renal failure (n = 28), or other chronic nonthyroidal disorders (n = 9). These patients had reduced mean serum total T3 (TT3) and free T3 (FT3) concentrations, normal total and free T4 levels, normal TSH values, and increased serum reverse T3 (rT3) concentration (with the exception of chronic renal failure patients, who had normal rT3 levels). Serum IL-6 concentration was increased above normal (i.e. > 100 fmol/L) in almost all NTI patients, especially in those with low T3 values (median value: 258 fmol/L, range 73-3210, vs 152 fmol/L, range < 12.5-460, in patients with normal TT3 values, p < 0.001). Serum IL-6 values in NTI patients were negatively correlated with serum FT3 values (r = 0.56, p < 0.001), and positively correlated with serum rT3 values (r = 0.78, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)