Thirty-two dogs subjected to 4 min of ventricular fibrillation were equally divided into four treatment groups: (a) immediate defibrillation (control); or 30 min of (b) standard CPR (SCPR), (c) simultaneous ventilation-compression CPR (SVC-CPR), or (d) open-chest CPR (OCCPR). After 30 min of CPR, restoration of spontaneous circulation was attempted using drug therapy and countershocks and the animals maintained for 24 h or until refractory hypotension occurred. During CPR, OCCPR yielded higher mean arterial and lower central venous pressures than either external method. Circulation was restored in all control dogs, and by 24 h they had nearly normal neurologic deficit scores. In the SCPR group, the heart was restarted in six dogs. Five of these dogs had severe neurologic damage and did not survive 24 h. The animal that survived 24 h, however, was nearly normal neurologically. Although circulation was restored in five SVC-CPR dogs, all were brain-dead and none survived 24 h. In the OCCPR group, seven animals survived 24 h and their neurologic deficit scores were not significantly different from control values. We conclude that OCCPR is greatly superior to SCPR and SVC-CPR with respect to preservation of the brain during resuscitation.