This study investigated the effects of normoxic (FIO2 = 0.21), hyperoxic (FIO2 = 1.0), and hyperoxic (FIO2 = 1.0) plus antioxidant pretreatment (tirilazad mesylate) [corrected] resuscitation on neurologic outcome following 9 min of normothermic (39 +/- 1.0 degrees C) cardiac arrest. Physiologic variables including arterial blood gases and neurologic outcome, which was assessed using a standardized scoring system, were followed over a 24-h period following resuscitation from cardiac arrest. Hyperoxically resuscitated dogs sustained significantly worse neurological deficit at 12 and 24 h (mean scores: 39 +/- 3 and 49 +/- 8, respectively) than did antioxidant pretreated hyperoxically resuscitated dogs (mean scores: 22 +/- 1, P = 0.0007 and 22 +/- 1, P = 0.004, respectively) and normoxically resuscitated dogs (mean scores: 28 +/- 4, P = 0.025 and 33 +/- 8, P = 0.041 respectively). These data suggest that oxidant injury has a major role in central nervous system dysfunction following successful resuscitation from 9 min of cardiac arrest. Also, resuscitation from cardiac arrest with hyperoxic FIO2's may contribute to and further exacerbate neurologic dysfunction.