The serum levels of soluble interleukin-2 receptors (s-IL-2R) and soluble CD8 antigens (s-CD8) were measured in 33 patients with Graves' disease (GD), 29 with toxic nodular goiter (TNG), 6 with toxic adenoma (TA), and 12 with hypothyroidism, as well as in 11 patients with infectious mononucleosis (known to have high s-IL-2R and s-CD8 levels) and 34 normal controls. Serum levels of T3 and T4, both total and free, and of TSH were simultaneously determined. s-IL-2R levels were significantly higher in all patients with hyperthyroidism (mean +/- SD, 3276 +/- 1273 U/mL for GD, 4183 +/- 1832 for TNG, and 1671 +/- 648 for TA) compared to normal control values (P less than 0.001 for GD and TNG and P less than 0.01 for TA), while in the euthyroid state they were within the normal range (535 +/- 240 U/mL). Hypothyroid patients had significantly lower s-IL-2R levels compared to normal controls (P less than 0.05). A positive correlation (P less than 0.001) between serum s-IL-2R levels and total/free T3-T4 levels was found in these groups of patients, while no correlation between s-CD8 levels and s-IL-2R/T3/T4 was found. These findings suggest an association between hyperthyroxinaemia and activation of human lymphocytes in vivo.