The electrophysiologic actions of epinephrine (10(-9) M, 10(-8) M, and 10(-7) M) were evaluated in canine Purkinje fibers pretreated with the class III antiarrhythmic drugs clofilium (10(-7) M) or d,l-sotalol (10(-6) M). Clofilium and d,l-sotalol prolonged action potential duration at 50% and 90% of repolarization without provoking early afterdepolarization (EAD) or delayed afterdepolarization (DAD). Subsequent administration of epinephrine provoked both bradycardia-dependent EADs and tachycardia-dependent DADs in clofilium-treated Purkinje fibers, with predominantly EADs observed in d,l-sotalol-treated Purkinje fibers. A temporary increase in Ca0(+2) from 1.35 mM to 5 mM suppressed both EADs and DADs. The data demonstrate facilitation of epinephrine-induced EADs and DADs by class III antiarrhythmic drugs. The acute suppression of both EADs and DADs observed following an acute increase in Ca0(+2) suggests inward Na(+)-Ca0(+2) exchange current as a basis for both EADs and DADs observed in the presence of class III antiarrhythmic drugs and epinephrine.