The placenta is a chimeric organ that produces all the components of the hypothalamic-pituitary Gh axis. We propose that placental Gh-releasing hormone (Ghrh) stimulates placental Gh-like hormones which in turn stimulate production of the insulin-like growth factors (Igfs), Igf-I and Igf-Ii, and these placental Igfs are important for growth and development of the placenta as well as the fetus. To test this hypothesis, pregnant rats were given either Ghrh antisera or preimmune sera ip from days 7–19 of gestation. Fetuses were killed on day 19, and Igf-I and Igf-Ii tissue and serum concentrations in the mother and fetus were measured by Ria. Igf-Ii receptor content was measured by Western analysis. Igf-I and Igf-Ii messenger (m) Rna levels were measured in the placentas as well as in the fetal livers. The Ghrh antibody titer was highest at day 19 of gestation but continued to be present through day 20 of postnatal development. Although placental weights did not differ, antibody-treated animals had higher placental Igf-I and Igf-Ii levels (I, 108 ± 6 (Sd); Ii, 126 ± 5 ng/g, respectively) vs. control animals (I, 88 ± 2.5 (Sd); Ii, 48 ± 11 ng/g) in pooled specimens. The Igf-Ii receptor was also up-regulated in placentas from antibody-treated mothers. The fetuses of antibody-treated (A) mothers were larger than the controls (C) (A, 2.615 g; C, 2.49 g, P < 0.05). Levels of both Igfs were significantly increased in livers of antibody treated fetuses (Igf-I: A, 15 ± 1 (Sd); C, 12 ± 0.8 ng/g; and Igf-Ii: A, 295 ± 10 (Sd); C, 233 ± 10 (Sd) ng/g). In addition, the concentration of the Igf-Ii receptor in liver of antibody-treated fetuses was also increased. Further, pooled fetal sera from antibody-treated fetuses had higher levels of Igf-Ii than controls (A, 950 ng/ml; C, 700 ng/ml), and the circulating Igf-Ii receptor was increased as measured by Western analysis. In the liver, Igf-Ii mrna levels of antibody-treated fetuses were increased to 117% of controls, whereas Igf-I mrna levels were undectable. The placenta showed no increase in placental lactogen or Gh mrna, whereas Igf-Ii and Ghrh mrna were slightly increased in antibody-treated animals. In conclusion, these data suggest that Ghrh may interact with the Igfs in a different fashion during prenatal development then during postnatal development. However, the relative roles of maternal and fetal hypothalamic Ghrh compared with placental Ghrh remain to be studied.