Previous studies have shown that hypoxia and severe repeated asphyxia modify the N-methyl-D-aspartate (NMDA) receptor, decrease Na+,K+-ATPase activity, and increase lipid peroxidation and free radical production. The present study investigates the effect of hyperoxic and normoxic reventilation following asphyxia in piglets on NMDA receptor activation, lipid peroxidation and free radical generation. Asphyxia was induced in 8 anesthetized and paralyzed piglets by discontinuing mechanical ventilation for 6-12 min until the heart rate was <60 bpm (mean pH<6.80, PCO2>120mmHg and PO2<5mmHg). After asphyxia, animals in Grp 1 (n=4) and Grp 2 (n=4) were reventilated with 21% oxygen and 100% oxygen for 20 min. The cerebral cortices were removed for analysis.3[H]MK-801 binding, an index of NMDA receptor activation, showed the Bmax (number of receptors) in Grp 1 and Grp 2 to be 1.32±0.13 and 1.57±0.34 pmol/mg protein (mean±SD). Kd for the same groups were 4.45±1.45 and 3.79±0.96 nM. Bmax and Kd in controls were 1.23±0.06 pmol/mg protein and 5.8±0.5 nM. Na+,K+-ATPase activity in Grps 1 and 2 were 23.5±0.9 and 24.4±3.9 μmol Pi/mg protein/hr, as compared to control(49.9±0.5, p<0.05). Lipid peroxidation products, conjugated dienes(0.07 vs. 0.05 μmol/g brain) and fluorescent compounds (0.78 vs. 0.54 μg quinine sulfate/g brain) were similar. Electron spin resonance spectroscopy performed after trapping spin adducts in α-phenyl-N-tert-butylnitrone for the detection of alkoxyl radical showed similar spin adduct signal height intensity (10.39 vs. 13.68 mm/g tissue). The results show that NMDA receptor activation, lipid peroxidation. Na+,K+-ATPase activity and alkoxyl radical generation were similar following reventilation with 100% and 21% oxygen. These data did not reveal immediate cerebral cellular dysfunction with either normoxic or hyperoxic reventilation following asphyxia. Since previous data have shown a 48 h delay in the appearance of neuronal membrane injury, the long term effect of reventilation with oxygen on neuronal membrane function remains unknown. (Funded by NIH HD-20337, MOD-6FY940135, UCP#R-506-93).