OBJECTIVE To characterize 1) pulmonary gas exchange, 2) pulmonary function, 3) lung fluid and tissue phospholipid content, and 4) thyroid hormone in the premature lamb (0.85 of term) after intra-amniotic administration of 100 micrograms of triiodothyronine (T3) 2 weeks before delivery. METHODS Nine fetal lambs were given 100 micrograms of intra-amniotic T3 under ultrasound guidance at 112 +/- 1 days' gestation and delivered at 126 +/- 1 days (term = 149 days). Five saline-injected animals served as controls. Arterial blood gases, pulmonary mechanics, and lung volumes were compared between groups for 1 hour after delivery. At delivery, tracheal fluid and blood was taken for T3, and thyroxine (T4) levels. Tracheal fluid and lung tissues were assayed for total phosphorus and disaturated phosphatidylcholine. RESULTS Triiodothyronine-treated lambs had significantly higher mean arterial pH and lower PCO2 than controls (P < .05) with a trend toward higher mean PO2. The dynamic lung compliance was increased by 54% with a 40% proportional increase in tidal volume and minute ventilation in the T3-treated group (P < .05). Functional residual capacity increased 69% (P < .05) without a change in specific compliance. The tracheal fluid and pulmonary phospholipids and tracheal fluid and plasma T3 and T4 levels were not different between the two groups. CONCLUSIONS A single 100 micrograms dose of antenatal T3 significantly improves neonatal gas exchange and lung compliance. The improvement in lung function was not accompanied by an increase in pulmonary surfactant production. It is inferred that T3 improved lung function via accelerated structural development of the lung with an alternative possible effect on parenchymal connective tissue matrix.