We performed a comparative study to determine whether acute administration of MgSO4, moricizine, and verapamil to conscious dogs with normal plasma magnesium levels (0.75 ± 0.06 mM) terminates ouabain-induced ventricular tachycardia (VT). This arrhythmia is dependent on triggered activity (TA) resulting from delayed afterdepolarizations (DADs). In animals with surgically induced complete atrioventricular (AV) block, monomorphic VT was induced by programmed ventricular stimulation during continuous intravenous (i.v.) infusion of ouabain. At the moment of drug administration, VT persisted for at least 20 min, while the rate was stable for at least 5 min. A single dose of MgSO4 (100 mg/kg i.v.) abolished only VTs with cycle lengths ≧320 ms (335 ± 10 ms); VTs with faster cycle lengths (300 ± 20 ms) were merely slowed, although the increase in plasma magnesium levels was considerable and comparable in both groups (3.9 ± 1.6 and 4.8 ±1.9 mM). In contrast, moricizine (2 mg/kg i.v.) and verapamil (0.5–1.0 mg/kg i.v.) terminated both fast and slow VTs. The cycle length of VT ranged from 280 to 320 ms (mean 300 ± 15 ms) for moricizine and 260–330 ms (mean 300 ± 25 ms) for verapamil. We conclude that (a) moricizine and verapamil are more effective than MgSO4 in terminating ouabain-induced VT; (b) MgSO4 has a direct pharmacologic effect on this arrhythmia that does not require the presence of magnesium deficiency to be effective; (c) the ability of MgSO4 to terminate ouabain-induced VT demonstrates inverse rate dependency; and (d) the mechanism of action of MgSO4 in affecting sustained monomorphic VT resulting from cardiac glycoside toxicity appears to be different from those of the other two drugs.