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Objective: We studied the effects of selenium (Se) treatment on serum anti-thyroid peroxidase (TPO) levels in Greek patients with Hashimoto's thyroiditis (HT)., Design: We prospectively studied 80 women with HT, median age 37 (range 24-52) years, for 1 year. All patients received 200 microg Se in the form of l-selenomethionine orally for 6 months. At the end of the 6-month period, 40 patients continued taking 200 microg Se (Group A) and 40 patients stopped (Group B). Serum thyrotropin (TSH), free triiodothyronine (FT(3)), free thyroxine (FT(4)), anti-TPO, and anti-thyroglobulin (Tg) levels were measured at baseline and at the end of each 3-month period., Main Outcome: There was a significant reduction of serum anti-TPO levels during the first 6 months (by 5.6% and 9.9% at 3 and 6 months, respectively). An overall reduction of 21% (p < 0.0001) compared with the basal values was noted in Group A. In Group B, serum anti-TPO levels were increased by 4.8% (p < 0.0001) during the second 6-month period., Conclusions: Our study showed that in HT patients 6 months of Se treatment caused a significant decrease in serum anti-TPO levels, which was more profound in the second trimester. The extension of Se supplementation for 6 more months resulted in an additional 8% decrease, while the cessation caused a 4.8% increase, in the anti-TPO concentrations.