To assess if cocaine alters cerebral glucose metabolism in the fetus, we infused cocaine 0.6 mg/min intravenously to 6 of 13 fetal sheep for the 55 min prior to measurement of glucose utilization by an autoradiographic method. Overall, local cerebral glucose utilization (LCGU) was lower in cocaine-exposed fetuses than in 7 controls (P = 0.058). In the cocaine-exposed fetuses, 33 of 34 structures had lower mean LCGU than in the comparable structures of control fetuses. In addition, the autoradiographs in 4 of 6 cocaine-exposed fetuses revealed thin, dark lines of increased glucose utilization within the central white matter of some frontal gyri which were not seen in any of the 7 control fetuses. These lines were distributed similarly to ones seen earlier in severely hypoxic newborn lambs. In fetal lambs, cocaine resulted in a generalized decrease in LCGU and a specific increase in glucose utilization in parts of cortical white matter of the frontal gyri, possibly secondary to local ischemia.