Conversion of sustained ventricular tachycardia (VT) to nonsustained VT may be a potent mode of antiarrhythmic drug action, whereas a drug's conversion of nonsustained VT to sustained VT could produce serious clinical complications. We tested the effects of two class Ic drugs [encainide (1, 2, and 4 microM) and propafenone (0.1, 0.3, and 0.6 microM)) and a class III drug (d-sotalol (25, 50, and 100 microM)] on the proportion of VT episodes that were sustained (duration greater than 1 min) in an acute in vitro model of reentrant VT in left ventricular (LV) epicardium: a Langendorff-perfused rabbit heart whose LV endocardial and midwall cells have been killed by a selective freezing procedure. Multiple VT episodes were generated by increasing the stimulation rate until self-sustained activity occurred. Some episodes spontaneously terminated in less than 1 min; others lasted longer and were terminated by transient cooling of the heart. Both encainide and propafenone increased the fraction of episodes of sustained VT in all preparations; the increase was significant in 4 of the 5 encainide preparations (p less than 0.02) and 4 of the 5 propafenone preparations (p less than 0.003). d-Sotalol, on the other hand, decreased the fraction of sustained VT in all preparations; the decrease was significant (p less than 0.002) in 4 of the 5 preparations. All 3 drugs increased the basic cycle length of pacing at which VT was induced and the cycle time of the resulting VT. These results of this new assay of drug action may be related to the drugs' different mechanisms of prolonging refractoriness.