Fas/FasL-mediated apoptosis results in the destruction of thyrocytes in chronic autoimmune hypothyroidism (CAIH). In this study, we examined the serum levels of soluble Fas (sFas) and soluble sFas ligand (sFasL) in euthyroid patients with chronic autoimmune hypothyroidism, who were taking levothyroxine (euthyroid, LT4-CAIH), to investigate the possible role of thyroid hormone therapy in down-regulation of apoptotic factors. Fifty euthyroid patients with CAIH on levothyroxine (median of duration 36 months, range 6-228 months) were compared with 75 age- and sex-matched healthy individuals. Serum levels of soluble Fas and soluble Fas Ligand, autoantibodies to thyroid peroxide and thyroglobulin were measured using ELISA. Serum levels of sFas were significantly higher in the euthyroid, LT4-CAIH group [median 9.12 ng/ml, interquartile range (7.86-10.72 ng/ml)] than in the controls [6.11 ng/ml (5.60-6.81 ng/ml)] (P < 0.0001). Compared with controls [80.33 pg/ml (68.22-103.70 pg/ml)], the euthyroid, LT4-CAIH group [125.71 pg/ml (106.11-149.48 pg/ml)] had significantly higher levels of sFasL (P < 0.0001). In a chronological study, there was no significant correlation between sFas, sFasL, and the duration of levothyroxine therapy. In conclusion, normalization of serum sFas and sFasL levels cannot be achieved during levothyroxine treatment in patients with CAIH. It appears that levothyroxine therapy has no important effect on down-regulation of apoptotic factors in CAIH. Thus, like thyroid autoantibodies, monitoring of serum levels of sFas/sFasL is not indicated during thyroid hormone therapy.