Free radical production in the brain of acutely anesthetized, exteriorized lamb fetuses (n = 11, gestational age = 135 d) was measured using spin trap methodology. Communications between the vertebral and carotid circulations were tied, producing a two-vessel supply to the brain. Flow probes and occlusion slings were placed around each carotid. The spin trap 2-ethyl-3-hydroxy-2,4,4-trimethyloxazolidine (OXANOH) was infused intermittently into one carotid at a constant rate, and blood samples were taken at intervals from the sagittal sinus. These samples were analyzed for the stable radical OXANO. using electron spin resonance spectrometry. Six animals were subjected to 30 min of complete cerebral ischemia, and five fetuses served as sham-operated control animals. During postischemic reperfusion radical formation increased 2-fold during the first 20 min. However, the elevation of OXANO. in the venous effluent from the brain did not start until the transient hyperemia had passed. It is thus concluded that the increase of OXANO. observed is caused by an augmentation of free radical production during reperfusion. Because the spin trap agent was infused directly into the arterial supply and recovered directly from the venous effluent of the brain, the site of production could be the brain tissue, the endothelial cells of the cerebral circulation, and activated leukocytes. This is the first demonstration of increased radical production from the fetal brain. It is noteworthy that it takes place despite oxygen tension of the reperfusing blood of only 3-3.5 kPa.