A randomized, placebo-controlled, masked study was conducted of the responses of thyroid parameters, cortisol, and the cardiovascular system to a single dose of triiodothyronine (T(3)) 24 h after birth, followed by a daily dose of thyroxine (T(4)) during 6 wk to infants <28 wk gestational age. Thirty-one infants were assigned to three groups: 1) group A: T(3) 24 h after birth plus daily T(4) during 6 wk; 2) group B: placebo T(3) and T(4) during 6 wk; and 3) group C: placebo T(3) and placebo T(4). T(4), free T(4), T(3), free T(3), reverse T(3), thyroid-stimulating hormone, and cortisol were measured in cord blood and on days 1, 3, 7, 14, 21, 42, and 56. Data on pulse rate, blood pressure, and cumulative dose of inotropic agents were collected. T(3) (0.5 microg/kg) resulted in a plasma increase until day 3. Thereafter, plasma T(3) levels were comparable between the groups. T(4), free T(4), and reverse T(3) were increased in groups A and B during the period of T(4) administration. Thyroid-stimulating hormone suppression was of shorter duration in group A. T(3) and T(4) administration did not have any effect on cortisol levels. We did not find any effects of T(3) or of T(4) administration on the cardiovascular system. A single injection of T(3) (0.5 microg/kg) given 22-26 h after birth only leads to a 2-d increase of T(3) levels and does not have effects on the cardiovascular system. This study does not support the use of T(3) according to our regimen in preterm infants.