Objective: To investigate the effect on thyroid hormone metabolism of the administration of thyroxine to very preterm infants. Design and methods: Two hundred infants of less than 30 weeks gestation were enrolled into a randomized, double-blind, placebo-controlled trial. Thyroxine (T 4 ) (at a fixed daily dose of 8 mg/kg birthweight) or placebo was started 12-24 h after birth and discontinued 6 weeks later. Plasma concentrations of T 4 , tri-idothyronine (T 3 ), reverse T 3 (rT 3 ), TSH, and thyroxine-binding globulin were measured weekly during trial medication and 2 weeks thereafter. Results: The T 4 and the placebo group each comprised 100 infants. Antenatal, perinatal, and postnatal clinical characteristics were comparable in both groups. T 4 and rT 3 were significantly increased in the T 4 group. TSH concentrations were depressed in the T 4 group and T 3 was significantly decreased, probably as a result of TSH depression. The T 4 /T 3 and T 4 /rT 3 ratios differed significantly between the two study groups. Conclusions: Daily T 4 administration during the first 6 weeks after birth to infants of less than 30 weeks gestation prevents hypothyroxinemia, but decreases plasma T 3 concentrations. Our finding possibly implies that very preterm infants should receive supplements of both T 4 and T 3 .