Summary: This study examines the effect of maternally injected glucocorticoid on the pattern of hjpoglycemia exhibited by rat pups with intrauterine growth retardation (IUGR). The majority of surgical procedures designed to produce small-for-gestational age (SG A) newborns for biochemical studies were carried out on days 18 and 19 of gestation because of favorable yields of pups with IUGR at those operative days. At birth, normal controls showed a mean ± SE plasma glucose value of 63 ± 2 mg/dl; mean glucose for the group with IUGR was significantly lower at 43 ± 2 mg/dl. There was a further decrease in the plasma glucose concentration of pups with IUGR at 2–4 hr of age, whereas values in the control littermates did not fall during this interval. Through the first 2 hr of neonatal life, 46% of the pups with IUGR exhibited plasma glucose values less than 40 mg/dl, whereas only 18% of the control littermates manifested hypoglycemia. During the 2–4-hr interval, the incidence of hypoglycemia in animals with IUGR increased to 91%; however, the incidence in controls remained at 18% from 2–4 hr and fell to 4% at 4–6 hr of age. At birth, the pups with IUGR had a lower mean liver weight compared to their control littermates, but glycogen concentration of liver was similar to the control mean ± SE of 25.7 ± 1.8 (IUGR = 22.2 ± 1.3 mg/g wet weight). Total hepatic glycogen stores, however, were markedly lower in dysmature rat pups (IUGR = 2.96 ± 0.17 mg; control = 7.23 ± 0.43 mg). Concentrations of plasma glucose at birth of individual control and IUGR animals were found to correlate significantly (r = 0.64, p < 0.001) with total liver glycogen content. The decline in plasma glucose values in pups with IUGR was not present in animals whose dams received glucocorticoid injection 24 and 48 hr before delivery. At 4–6 hr of age, for instance, the mean plasma glucose concentration in the corticoid-treated IUGR group (70.1 ± 6.9 mg/dl) approximated that of the control group. Instead of the 91% incidence of hypoglycemia noted in the nontreated dysmature pups, an incidence of 55% was found at 2–4 hr of age in offspring of mothers given glucocorticoid. At 4–6 hr, the treated group showed an incidence of 18% compared to a 67% figure in the nontreated IUGR animals. The concentration of liver glycogen in these animals also differed in that the treated IUGR pups showed significantly higher values (26.9 ± 1.7 mg/g wet weight, mean ± SK) than nontreated progeny. It is concluded that antenatally administered corticosteroids influence the development of neonatal hypoglycemia in the dysmature rat pup and that the major effect is not at birth, but during the 2–4-hr period of neonatal life. Speculation: These data indicate that hypoglycemia may be prevented by antenatally administered steroids in an animal model of the SGA infant and raise the possibility of prenatal intervention in susceptible fetuses. The protective mechanism that manifests itself in early neonatal life may be attributable to better utilization of gluconeogenic substrates and induction of key enzymes in developing liver.