Stromal-derived factor 1 (SDF-1) and CXCR4 comprise a unique chemokine/chemokine receptor pair, exhibiting important functions in morphogenesis and growth regulation as well as attractant properties on T lymphocytes. No data are available on SDF-1 and CXCR4 in normal or pathological thyroid tissues. SDF-1, CXCR4, and CD18 messenger ribonucleic acid (mRNA) as a marker of leukocytic infiltration were quantified in tissues affected by thyroid adenoma (n = 11) and Graves' disease (GD; n = 16) using competitive RT-PCR. SDF-1 mRNA levels differed significantly between autonomous adenomas and the corresponding normal tissue, but not in GD between patients with low or high leukocyte infiltration, thyroid peroxidase, and TSH receptor autoantibodies, respectively. We found a strong correlation between CXCR4 and CD18 mRNA, which indicates CXCR4 expression by leukocytes. To define the cellular source of SDF-1 and CXCR4 in thyroid tissue, we examined various thyroid-derived cells. Fibroblasts are the most potent producers of SDF-1, although thyrocytes also secrete SDF-1 in vitro. Leukocytes showed very weak SDF-1 mRNA levels and no secretion of the chemokine. Immunohistology confirmed and extended these results; SDF-1 expression was found in fibroblasts, but not or very weakly in CD45(+) leukocytes and thyrocytes. Only leukocytes were CXCR4(+). As examined by flow cytometry, the number of CD3(+) T cells expressing CXCR4 is significantly higher in the thyroid than in peripheral blood. SDF-1 seems to be involved in thyroid tissue homeostasis in thyroid adenoma, but not in the maintenance of lymphocytic infiltration in GD.