The concentrations of plasma glucose, insulin, growth hormone, and immunoreactive growth hormone-like substance in subhuman primate fetal and maternal plasma were examined after the intravascular administration of glucose, arginine, or tolbutamide to the fetus. Cannulation of interplacental vessels permitted studies on the fetus in utero without disruption of fetal-placental-maternal anatomic integrity. Single glucose injections, glucose infusions, and arginine infusions into the fetus did not alter fetal plasma insulin concentrations. In contrast, tolbutamide injections elicited an immediate 3-4-fold increase in fetal plasma insulin concentrations. A bidirectional placental transfer of insulin was demonstrated with the use of simultaneously injected insulin-(125)I to the mother and insulin-(131)I to the fetus. Simian fetal plasma contained a substance which cross-reacted with immunologic identity to human growth hormone. In contrast, simian maternal plasma and amniotic fluid reacted with immunologic nonidentity to human growth hormone. Although glucose administration to the fetus did not suppress nor did arginine infusion consistently augment fetal plasma growth hormone levels, the latter were observed to vary in individual experiments. The plasma responses to the same stimuli in the neonate were also examined. In contrast to the fetal experiments, glucose injection in the neonate elicited a delayed rise in the concentration of plasma insulin. Similar to the fetus, the plasma concentration of insulin increased after tolbutamide injection and did not change in response to arginine infusion. The initial concentrations of neonatal plasma growth hormone were significantly lower when contrasted with the initial fetal plasma levels. There was no difference in the responsiveness of the fetal and neonatal growth hormone-releasing mechanisms when challenged by glucose or arginine infusion. The data indicate that the fetal plasma concentration of growth hormone is labile, that fetal growth hormone metabolism may differ from that in the neonate, and that pancreatic islet cell responsiveness rapidly changes after delivery.