Abstract Standard drug therapy for asystole during cardiac arrest includes epinephrine, atropine, and calcium chloride (CaCl). Recent studies have shown that ventricular fibrillation (VF) can appear to be asystole when recorded from the chest surface. To determine the efficacy of these drugs and electrical countershock for asystole, a group of 83 adult nontraumatic cardiac arrest victims (55 men, 28 women, mean age of 64 ± 14 years) were studied. Asystole appeared at some time during arrest in 44 patients (53%) and was the initial rhythm in 24 (29%). The rate of survival to hospital discharge was significantly higher in patients whose initial rhythm was VF (46%) than in patients whose initial rhythm was asystole (0%). Epinephrine, CaCl and atropine infrequently changed the rhythm from asystole. Electrical countershock infrequently altered the rhythm from asystole when it appeared as the initial rhythm. However, countershock was significantly more effective than epinephrine ( P < 0.003), atropine ( P < 0.04), or CaCl ( P < 0.03) in altering the rhythm from asystole, which appeared later in resuscitation. Ventricular fibrillation was the most common rhythm appearing after countershock for asystole. Countershock appears to be superior to epinephrine, CaCl, and atropine for treating asystole during the course of resuscitation, suggesting that the rhythm diagnosed as asystole may actually be VF in many cases.