Countershock of prolonged ventricular fibrillation is usually followed by asystole or a nonperfusing rhythm. Data from three laboratory investigations indicate that administration of epinephrine and cardiopulmonary resuscitation (CPR) preceding countershock of prolonged ventricular fibrillation significantly improves cardiac resuscitation outcome compared with immediate countershock (relative risk reduction of failed resuscitation, 0.61). Preliminary investigations indicate that a similar improvement is not observed when the ventricular fibrillation period is of shorter duration, e.g., 5 mins. This time interval is probably at the lower limit at which CPR preceding shock of ventricular fibrillation provides benefit in terms of cardiac resuscitation. A single clinical trial of "CPR first" supports the use of a brief period of CPR before countershock of prolonged ventricular fibrillation. Additional trials with and without epinephrine are anticipated.