Summary125I-Tyr insulin (125I-Tyr Ins) was injected into the vitelline vein of rat fetusesin uteroafter 17, 19, or 21 days of gestation. Three min later, the weight and radioactivity of various organs and of the remaining carcass were measured. A radioactivity concentration index (RCI) was calculated by dividing the specific activity of each organ by that of the whole feto-placental unit. In each of the three age groups studied, the RCI indicated that125I-Tyr Ins was concentrated in several organs, notably the liver and kidneys. The lungs also concentrated the labeled hormone; however, only the youngest fetuses revaled significantly elevated levels. Lung RCIs were 1.68 ± 0.27, 0.67 ± 0.12, and 0.85 ± 0.18 after 17, 19, and 21 days of gestation, respectively. Three, 9 and 15 min after125-I-Tyr Ins injection, the lungs and liver of 17-day postcoitum fetuses were homogenized and then subjected to gel chromatography. During the 15 min period of investigation, the percentage of intact labeled hormone in the liver and lungs decreased while the percentage of125I-tyrosine increased.Autoradiographs of the fetal lungs indicated that the pseudoglandular cells bound125I-Tyr Ins (surface density of grains 9 min after125I-Tyr Ins alone, 1.71 ± 0.22) and that this process was inhibited by coinjection of 100 mU unlabeled insulin (surface density of grains, 0.50 ± 0.16;P< 0.001). At 9 min, the surface density of grains on the bronchial tubes was only six times less than that of the hepatocytes of the same fetuses. It was concluded that epithelial lung cells during the pseudoglandular stage are equipped with numerous insulin receptors and appear capable of degrading insulin. The concentration of receptors markedly decreased at a later stage of lung development.