The optimal inhaled oxygen fraction for newborn resuscitation is still not settled. We hypothesized that short-lasting oxygen ventilation after intrauterine asphyxia would not cause arterial or cerebral hyperoxia, and therefore be innocuous. The umbilical cord of fetal sheep was clamped and 10 min later, after delivery, ventilation with air (n = 7) or with 100% oxygen for 3 (n = 6) or 30 min (n = 5), followed by air, was started. Among the 11 lambs given 100% oxygen, oxygen tension (PO2) was 10.7 (1.8-56) kPa [median (range)] in arterial samples taken after 2.5 min of ventilation. In those ventilated with 100% oxygen for 30 min, brain tissue PO2 (PbtO2) increased from less than 0.1 kPa in each lamb to individual maxima of 56 (30-61) kPa, whereas in those given oxygen for just 3 min, PbtO2 peaked at 4.2 (2.9-46) kPa. The maximal PbtO2 in air-ventilated lambs was 2.9 (0.8-5.4) kPa. Heart rate and blood pressure increased equally fast in the three groups. Thus, prolonged ventilation with 100% oxygen caused an increase in PbtO2 of a magnitude previously only reported under hyperbaric conditions. Reducing the time of 100% oxygen ventilation to 3 min did not consistently avert systemic hyperoxia.