The effect of fetal hypoglycemia and hypoinsulinemia on fetal rat hepatic glucose-6-phosphatase activity was studied. Fetal hypoglycemia and hypoinsulinemia were produced by inducing maternal hyperinsulinemia and hypoglycemia secondary to the exogenous administration of insulin via implantation of osmotically driven minipumps on day 15 of gestation into 15 experimental animals. 13 animals served as sham-operated controls. Cesarean sections were performed on day 20 or 21 of gestation under pentobarbital anesthesia. Liver glucose-6-phosphatase activity was increased in the hypoinsulinemic fetuses. In contrast, the hyperinsulinemic mothers had suppressed hepatic glucose-6-phosphatase activity. Hypoinsulinemia would appear to be the primary stimulus for enhanced fetal glucose-6-phosphatase in this model.