The present studies were performed to determine the effect of normal levels of insulin on fetal glucose metabolism and to measure the acute changes in insulin secretion and concentration that occur in response to a hyperglycemia stimulus. In fetal sheep, infusion of somatostatin alone decreased fetal insulin concentration 4 microU/ml (33%) from the basal value without a significant change in fetal glucose concentration, umbilical glucose uptake (UGU), or fetal glucose utilization rate (GUR). Glucose plus somatostatin infusion produced a significantly lower insulin concentration (54% lower, P less than 0.005) and GUR (22% lower, P less than 0.05) at glucose concentration approximately 40 mg/dl compared with glucose infusion alone. No significant difference was seen at glucose concentration of approximately 30 mg/dl. These results indicate that fetal glucose metabolism is responsive not only to changes in glucose but also insulin concentrations; however, a relatively large change in insulin (greater than 5 microU/ml) is necessary to produce a measurable response. These quantitative aspects of fetal insulin effect must be considered when assessing the role of insulin in the regulation of fetal glucose metabolism.