Objective: To address the influence of thyroid hormones on circulating markers of cell-mediated immune response in an in vivo human model. Subjects and design: Twenty-two patients with stage I differentiated thyroid carcinoma were studied on the last day of thyroxine suppressive treatment, 4–7 days after withdrawal, and the day before whole body scanning. Three patients were excluded because of residual disease. Twenty euthyroid individuals served as controls. Serum thyrotrophin and thyroid hormones were measured by an immunometric assay, circulating cytokines by enzyme-linked immuno-sorbent assay and lymphoid populations by flow cytometry. Results: Thyroid function in patients changed from subclinical or mild hyperthyroidism at the first visit, to a situation of normal circulating levels of free thyroxine and triiodothyronine at the second, ending in a state of overt hypothyroidism. Thyroxine suppressive treatment in patients increased serum interleukin-18 concentrations (IL-18, mean±s.d., 280±122 vs 183±106 pg/ml, F = 3.192, P = 0.029), soluble interleukin-2 receptor levels (sIL-2R, 4368±1480 vs 2564±846 pg/ml, F = 21.324, P < 0.001), and the percentage of natural killer (NK) cells in peripheral blood (15.9±8.6 vs 10.5±3.6%, F = 4.977, P = 0.004) compared with controls. After thyroxine withdrawal, serum levels of IL-18, sIL-2R and the percentage of NK cells decreased progressively. Conclusion: Our present results suggest that thyroid hormones modulate the cell-mediated immune response in humans.