Propafenone, a new antiarrhythmic agent, was utilized in 30 patients with diverse heart disease who presented with sustained hemodynamically unstable ventricular arrhythmia. Drug efficacy was judged by means of ambulatory electrocardiographic monitoring and exercise testing. Nine patients additionally had invasive electrophysiologic studies. Seventeen patients (57%) responded to therapy as judged by monitoring and 21 patients (70%) responded to therapy as judged by exercise testing. When both methods were considered, 16 patients (53%) responded. The acute drug test predicted the result of maintenance therapy in 91% of patients. Seven of nine patients who had electrophysiologic testing responded based on this technique, and in all cases the results were concordant with the noninvasive evaluation. Serum blood levels did not correlate with antiarrhythmic effect. In patients with myocardial impairment, echocardiographic assessment of left ventricular function indicated a decrease in ejection fraction during propafenone therapy (32 versus 24%, p less than 0.05), while no change was observed in patients with normal left ventricular function. Side effects occurred in nine patients and included exacerbation of congestive heart failure, development of conduction abnormalities and aggravation of arrhythmia, each occurring in two patients. Ten patients who continued on long-term propafenone therapy for an average of 10 months (range 3 to 13) have remained free of arrhythmia and side effects. Propafenone needs to be employed with caution in patients with congestive heart failure or evidence of conduction system disease.