Recent studies on cerebral resuscitation following an ischemic anoxic insult suggest that both inadequate reperfusion and direct neuronal death are partially initiated by calcium entry into vascular smooth muscle and neurons. To investigate the effects of calcium blocking agents on cerebral resuscitation, a controlled perfusion arrest model with cardiopulmonary bypass was used. Post-resuscitation regional cerebral cortical blood flow (rCCBF) and intracranial pressures (ICP) were monitored in five control dogs and in 12 study dogs resuscitated after a prolonged (20-minute) cardiac arrest. The resuscitation included dexamethasone and three agents thought to be calcium entry antagonists and to offer potential cerebral protection after complete prolonged cerebral ischemic anoxia.Prearrest rCCBF measured by a thermal dilution method with a thermistor placed on the cerebral cortex was 2.0 ± 0.6 (S.D.) ml/gm/min on bypass at 100 mm Hg mean arterial pressure. Twenty minutes after resuscitation was begun, the rCCBF in ml/min/gm were: controls 1.1 ± 0.3; dexamethasone (2 mg/kg) 1.2 ± 0.4; MgSO4(100 mg/kg) 1.8 ± 0.5; verapamil (0.15 mg/kg) 1.9 ± 0.4; and lidoflazine (1 mg/kg) 1.5 ± 0.3. Ninety minutes following the beginning of resuscitation the rCCBF were: controls 0.1 ± 0.1; dexamethasone 0.1 ± 0.1; MgSO4, 1.7 ± 0.3; verapamil, 1.9 ± 0.4; and lidoflazine, 1.5 ± 0.3 ml/gm/min.Thus the Ca2+entry antagonists maintained cerebral blood flow at 20 and 90 minutes following a prolonged ischemic anoxic insult. Dexamethasone was no better than control. These data suggest that calcium entry blockers can maintain rCCBF and may have a significant role in cerebral resuscitation following cardiac arrest.