Previous studies in the fetal lamb have demonstrated that hyperglycemia stimulates the fetal metabolic rate. The present study examined the effects of chronic fetal hyperglycemia on fetal cerebral metabolic rate and electrocortical activity. Nine chronically instrumented fetal lambs had measurements of cerebral blood flow and cerebral uptake/excretion of oxygen, glucose, lactate, and beta-hydroxybutyrate taken before and during a 48-h fetal glucose infusion. Electrocortical activity was also recorded. The fetal arterial glucose concentration was 19.8 +/- 2.0 mg/dl before glucose infusion and 48 +/- 4.5 to 54.6 +/- 6.6 mg/dl during the infusion period. Cerebral blood flow and cerebral glucose and oxygen uptake increased by 219, 209, and 171%, respectively, by the end of the infusion period. There was a linear relationship between the fetal arterial glucose concentration and cerebral blood flow and cerebral glucose and oxygen uptakes. The electroencephalogram showed significant slowing with increases in the cerebral metabolic rate. These findings suggest that fetal hyperglycemia is associated with significant metabolic stimulation of the brain.