SummaryAdministration of thyrotropin-releasing hormone (TRH) to pregnant rabbits at 25 and 26 days of gestation results in increased pulmonary surfactant production by the fetus at 27 days (full term is 31 days). There was 60% more total phospholipid and 150% more phosphatidylcholine (the major component of surfactant) in the lung lavage from the fetuses in the treated group than in that from the controls. Lung lavage from the fetuses in the treated litters contained 13.4 ± 1.6 μg of total phospholipid phosphorus/g lung dry wt and 5.6 ± 1.1 μg of phosphatidylcholine phosphorus while that from the fetuses in the control litters contained only 8.2 ± 1.1 μg and 2.2 ± 0.4 μg, respectively. The phosphatidylcholine/sphingomyelin ratio increased from 1.0 in the lavage from the controls to 2.2 in that from the treated group. These changes in lung lavage phospholipid content and composition are in the direction of increased lung maturation. TRH administration had no effect on the incorporation of choline into phosphatidylcholine in fetal lung slices. These data suggest that TRH stimulates surfactant release rather than synthesis.SpeculationTRH has a physiologic role in fetal lung maturation and surfactant production. It may potentially be used in the prevention of the respiratory distress syndrome in humans.