Summary 125 I-Tyr insulin (lZ5I-Tyr Ins) was injected into the vitelline vein of rat fetuses in utero after 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 that lZ5I-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 f 0.27,0.67 f 0.12, and 0.85 rf: 0.18 after 17, 19, and 21 days of gestation, respectively. Three, 9 and 15 min after 125-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 of 1251-tyrosine increased.Autoradiographs of the fetal lungs indicated that the pseudoglandular cells bound lZ51-Tyr Ins (surface density of grains 9 min after 1251-Tyr Ins alone, 1.71 f 0.22) and that this process was inhibited by coinjection of 100 m u unlabeled insulin (surface density of grains, 0.50 f 0.16; P < 0.001). At 9 rnin, the surface .