This study was to examine the effects of hypoglycemia on the brain metabolism of severe intrauterine growth retardation (IUGR) rat pups. IUGR pups were produced by ligating one of the uterine arteries of the dams. The pups on the opposite uterine horn were used as the control. They were delivered by cesarean section on day 21 and received regular insulin 5 units/kg or equivalent volume of normal saline at 40 min of age. The plasma glucose, lactate, blood gas values and brain glucose, lactate, and ATP contents were determined at 5 and 100 min of age. The IUGR pups had higher plasma and brain lactate concentrations than the control throughout the study period. They had lower plasma glucose, oxygen and pH values, brain glucose and ATP contents than control at 5 min of age. Despite insulin-induced hypoglycemia, brain ATP contents of the IUGR recovered to normal levels at 100 min of age when the oxygenation and pH improved. These data indicate that the brain energy metabolism of IUGR rat pups was suppressed by asphyxia and hypoglycemia. However, even in the continuing presence of hypoglycemia, brain energy metabolism returned to normal. The recovery is probably related to better oxygenation and utilization of alternative energy fuels, such as lactate.