We studied the effects of maternal uterine artery ligation on fetal rat tissue glucose utilization (GU). Unilateral uterine artery ligations were performed on the 19th d of gestation (term 21.5 d) and 2-[3H]deoxy-D-glucose was used to measure GU of placenta, liver, brain, muscle, kidney, and heart from fetuses in the ligated (IUGR) and nonligated (control) uterine horns 24 and 48 h after the procedure. At both periods, IUGR fetuses weighed significantly less and had lower fetal/maternal plasma glucose ratios than controls. Twenty-four h after ligation, placenta, liver, brain, and muscle from IUGR fetuses had lower relative GU rates than corresponding tissues from control fetuses (p less than 0.01-0.05). However, at 48 h, IUGR liver, muscle, kidney, and heart had higher relative GU rates than control tissues (p less than 0.01-0.05). The lower GU of IUGR fetal tissues observed at 24 h postligation was likely related to the acute decrease in fetal glucose availability. Other factors, such as hypoxemia and acidosis, that affect cellular metabolism may also have led to lower GU rates. The increase in GU by IUGR tissues at 48 h occurred despite a persistence of low fetal glucose concentrations and can be explained by either: 1) an attempt by IUGR fetal tissues to compensate for the persistently low plasma glucose; 2) an increased demand for metabolic fuel for repair processes; or 3) a less efficient use of glucose due to alterations in cellular respiration. We speculate that this increase in fetal tissue GU may be partially responsible for the supranormal glucose requirements seen in small-for-gestational-age newborns.