The effects of prenatal exposure to ethanol on glucose utilization in specific laminae of mature rat cerebral cortex were examined. Pregnant hooded rats were fed a liquid diet containing 35% ethanol-derived calories (E) or pair-fed an isocaloric liquid control diet (C) on gestational days 7-21. The cytoarchitecture of motor areas 4 and 6/8 and of somatosensory areas 3 and 2 of 105 day old, male pups was examined in Cresyl violet-stained sections. The glucose utilization of these cortical regions was assessed using a 2-deoxyglucose autoradiographic technique. Overall, cortex was significantly thinner (5-10%) in E-treated rats than in C-treated rats, but with few exceptions, the thickness of individual laminae was not significantly affected by prenatal treatment. Despite these small structural differences, the overall glucose utilization in areas 4, rostral 6/8 3, and 2 of E-treated rats was significantly less (21-24%) than in C-treated rats. Layer IV was the most affected by the prenatal ethanol exposure (29%) and layers I and VI were the least affected (14-22%). The metabolism of caudal area 6/8 was not significantly affected by gestational exposure to ethanol. These results indicate that thalamic and callosal connections and corticospinal projection neurons are specifically affected by prenatal exposure to ethanol. Such alterations may underlie the learning deficits and motor dysfunction characteristic of fetal alcohol syndrome.