CXC chemokine ligand 10 (CXCL10), an interferon-gamma-inducible chemokine associated with Th1-mediated immune responses, has been proposed as a marker of inflammation in autoimmune diseases. We measured serum CXCL10 concentrations in 223 consecutive patients with newly diagnosed autoimmune thyroiditis (AT), 97 euthyroid controls, and 29 patients with nontoxic multinodular goiter and related this parameter to the clinical phenotype. The three groups were similar in gender distribution and age; among the AT patients, 24% had subclinical hypothyroidism. Serum CXCL10 level was significantly higher in AT patients (157 +/- 139 pg/ml) than in controls (79 +/- 38) or patients with multinodular goiter (90 +/- 32; P < 0.0001). Among patients with AT, CXCL10 levels were significantly higher in those with a hypoechoic ultrasonographic pattern and hypothyroidism. In a multiple linear regression model including age, thyroid volume, hypoechogenicity, hypervascularity, TSH, free T(4), and antithyroid peroxidase, only age (standardized coefficient = 0.39; P = 0.0001) and TSH (standardized coefficient = 0.41; P < 0.0002) were significantly related to serum CXCL10 levels. We conclude that circulating CXCL10 is increased in patients with AT and is associated with hypothyroidism. CXCL10 may be regarded as a marker of a more aggressive thyroiditis leading to thyroid destruction.