We tested whether reoxygenation with 100% O(2) for 5 min after experimental asphyxia in newborn piglets was as efficient as 100% O(2) for 20 min compared with room air. Forty-one anesthetized piglets, 1-3 d old, were randomized to cerebral hypoxemia-ischemia-hypercapnia (HIH) or control (n = 5). HIH was achieved by ventilation with 8% O(2), temporary occlusion of the common carotid arteries, and adding of CO(2). After 25 min, reoxygenation-reperfusion was started with 100% O(2) for 20 min (group 1, n = 12), 100% O(2) for 5 min (group 2, n = 12), or 21% O(2) (group 3, n = 12). All piglets were observed for 2 h. During reoxygenation-reperfusion, significantly higher blood pressure and more complete restoration of microcirculation (laser Doppler flow) in the cerebral cortex was found in both groups reoxygenated with 100% O(2) compared with 21% O(2) (regional cerebral blood flow >or=100% versus 70% of baseline, p = 0.04). Reoxygenation with 100% O(2) for 5 min was as efficient as 20 min. Oxygen delivery in cortex was significantly higher in groups 1 and 2 compared with group 3 (p = 0.03), but there were no significant differences in cerebral metabolic rate for oxygen. In the striatum, no significant differences in flow or extracellular glutamate, glycerol, and lactate/pyruvate ratio were found between the groups. In conclusion, after experimental asphyxia, newborn piglets can be reoxygenated as efficiently with 100% O(2) for only 5 min as 100% O(2) for 20 min compared with room air.