The factor(s) regulating fetal growth remain obscure and classic hormones appear not to be involved. Fetal size correlates with fetal SM-C levels; however, fetal growth hormone appears to have no effect either on fetal SM-C or fetal growth. Placental lactogen has been suggested as a modulator of fetal somatomedins. To assess this possibility in the sheep model, time-dated pregnant ewes with singleton fetuses (n=7) underwent fetal arterial catheterization at 111±3 d of gestation (term=150 d). Daily blood samples were obtained from each fetus until parturition or death. (Mean survival=20 d). Serum samples were assayed for both placental lactogen and SM-C. There was no correlation between placental lactogen and SM-C during the study period (r=.03, n=82). A second group of fetuses (n=5) underwent single umbilical artery ligation at 111±3 d of gestation. This procedure results in markedly elevated levels of placental lactogen in the fetus. Chronically catheterized animals were sampled daily and samples were assayed for both placental lactogen and SM-C. Despite the increased plasma placental lactogen levels in these single umbilical artery ligated fetuses, there was no demonstrable correlation between plasma placental lactogen and SM-C concentrations (r=.03, n=66).Conclusion: Somatomedin-C levels in fetal sheep are independent of serum placental lactogen levels during the third trimester.