Summary: Somatomedin (SM) activity was measured by a placental membrane receptor assay using 125I-labeled somatomedin A, as radioligand in serum samples obtained from 33 ovine fetuses, 14 neonatal lambs, 8 pregnant, and 3 postpartum ewes. The mean serum concentration of SM activity in eight adult rams was 2.06 ± 0.12 U/ml. In fetal sheep, SM activity was detected at 66 days gestation (term 147 days), in the youngest fetus studied. Before 100 days of gestation, SM was lower (P < 0.001) in fetal sheep (1.08 ± 0.18 U/ml) than in adult rams. In fetuses between 101 and 125 days. SM rose (P < 0.001) to 2.64 ± 0.32 U/ml. In late gestation fetal serum SM fell but during the neonatal period it rose to 3.38 ± 0.3 U/ml, higher (P < 0.01) than that in adult rams. Serum SM activity in the pregnant ewe prior to 100 days was 1.01 ± 0.11 U/ml, increased (P < 0.05) to 1.75 ± 0.21 U/ml between 125 days and term, and rose further to 2.56 ± 0.32 U/ml in the postpartum period. Maternal concentrations of serum SM in late gestation were significantly less than in the fetus. Gel chromatog-raphy of fetal, maternal, and neonatal sera indicated that over 90% of SM activity circulated in high-molecular weight form. The rise in SM activity in fetal serum between 100 and 125 days parallels the rise in fetal growth hormone and prolactin concentrations; however, in maternal serum the increase in SM activity is associated with rising maternal chorionic somatomammotropin concentrations.Speculation: Somatomedin is present in fetal ovine serum and in late gestation may be generated mainly by fetal pituitary hormones. In contrast, somatomedin in the pregnant ewe appears to be regulated by chorionic somatomammotropin.