To study whether room air is as effective as 100% O2in resuscitation after hypoxia, hypoxemia (Pao22.3–4.3 kPa) was induced in newborn pigs (2–5 d old) by ventilation with 8% O2in nitrogen. When systolic blood pressure had fallen to 20 mm Hg, animals were randomly reoxygenated with either 21% O2(group 1, n - 9) or 100% O2(group 2, n = 11) for 20 min followed by 21% O2in both groups. Controls (group 3, n = 5) were ventilated with 21% O2throughout the experiment. Base deficit peaked at 31 ± 5 mmol/L (mean ± SD) for both hypoxic groups at 5 min of reoxygenation and then normalized over the following 3 h. There were no statistically significant differences between the two groups during reoxygenation concerning blood pressure, heart rate, base deficit, or plasma hypoxanthine. Hypoxanthine peaked at 165 ± 40 and 143 ± 42 μmol/L in group 1 and 2 (NS), respectively, and was eliminated monoexponentially in both groups with an initial half-life for excess hypoxanthine of 48 ± 21 and 51 ± 27 min (NS), respectively. Blinded pathologic examination of cerebral cortex, cerebellum, and hippocampus after 4 d showed no statistically significant differences with regard to brain damage. We conclude that 21% O2is as effective as 100% O2for normalizing blood pressure, heart rate, base deficit, and plasma hypoxanthine after severe neonatal hypoxemia in piglets and that the extent of the hypoxic brain damage is similar in the two groups.