The fetal lung responds to beta-receptor agonists with a release of surfactant from type II alveolar cells, if such stimulation were intense or long-lasting, the supply might become depleted and, while the supply is being restored, there could be a surfactant deficiency. With experiments on pregnant rabbits, this hypothesis was put to the test and found to be true. At a gestational age of 27.75 days, fetuses received the beta 2-receptor agonist terbutaline, 0.1 or 0.01 mg intramuscularly, or saline only. At the same stage of pregnancy, other does were infused with 7.2 to 9.6 mg of terbutaline or given Ringer's solution. The fetuses were put to death at intervals of 1 to 48 hours, and the lungs were examined. At 1 hour and also at 2 and 3 hours after injection of 0.1 mg of terbutaline, pressure-volume loops demonstrated improved compliance and stability compared to those of controls, but at 24 hours the situation was reversed. At 48 hours there was no difference. At 12 hours from the start of the infusion, pressure-volume loops clearly showed that fetuses of does receiving terbutaline were at a disadvantage. We conclude that terbutaline depleted surfactant stores and, while these stores are being replenished, there is a surfactant deficiency in the alveolar space. Phospholipid analysis supported our conclusion.