Clinically, treatment of pregnant women at risk of preterm delivery with synthetic glucocorticoids accelerates fetal maturation. This study investigated the effect of maternal dexamethasone treatment, in clinically relevant doses, on plasma thyroid hormone concentrations and tissue deiodinase activities (D1, D2 and D3) in ewes and their fetuses. From 125 days of gestation (term 145 ± 2 days), pregnant ewes were injected twice i.m. with either saline (2 ml of 0.9% NaCl, n = 11) or dexamethasone (2 x 12 mg in 2 ml of saline, n = 10) at 24 h intervals. Maternal dexamethasone treatment increased plasma triiodothyronine (T₃) and reverse T₃ (rT₃), but not thyroxine (T₄), concentrations in the fetuses. In the dexamethasone-exposed fetuses, hepatic D1 activity was higher, and renal and placental D3 activities were lower, than in the saline-exposed fetuses. In the ewes, plasma concentrations of T₃ and T₄ were reduced, and rT₃ increased, by dexamethasone treatment without any change in tissue deiodinase activity. Therefore, maternal dexamethasone treatment has different effects on the thyroid hormone axis of the pregnant ewe and fetus. In the fetus, the dexamethasone-induced rise in circulating T₃ may be due to both increased hepatic production of T₃ from T₄, and reduced clearance of T₃ by the kidney and placenta. Changes in T₃ bioavailability may mediate some of the maturational effects of antenatal glucocorticoid treatment in the preterm fetus.