Cell-mediated immunity is important in the pathogenesis of Graves' disease. Activation of T cells is apparently associated with the release of soluble CD8 (sCD8) and CD4 (sCD4) molecules from the corresponding T cell subset. To test the possibility that the concentrations of these molecules may be related to Graves' disease activity, we measured serum sCD8 and sCD4 concentration in 58 Graves' patients using ELISA technique before and after treatment with methimazole as well as in 10 patients with toxic nodular goiter. sCD8 was significantly elevated in thyrotoxic patients [609.9 +/- 118 (SD) U/ml] compared to controls (264.1 +/- 98.8, p < 0.001) and normalized when patients became euthyroid as a result of methimazole treatment (278.7 +/- 89.1). The mean sCD8 concentration in the patients with toxic nodular goiter was 302 +/- 28 U/ml, no different from control. The sCD4 level in the Graves' disease group was not different from control values and did not change significantly with treatment. Correlations were found between the levels of serum thyroid hormone(s) and sCD8 concentration but not with anti-TSH receptor antibodies in the 50 patients with Graves' disease. In addition, serum sCD8 studied prospectively in eight patients after discontinuation of methimazole, increased before the rise in serum T4, and well before the clinical relapse of thyrotoxicosis. It is concluded that sCD8 is a useful marker for the activation of CD8+ cells in Graves' disease.