The effectiveness of oral propafenone was evaluated for the treatment of ventricular premature complexes (VPCs) in 12 patients, using a single-blind, dose-ranging trial followed by a double-blind comparison with placebo, and then an open-label, long-term protocol. During dose ranging, 8 of 12 patients achieved greater than or equal to 80% suppression of total VPCs (mean 83%) (p less than 0.01 vs single-blind placebo). Paired VPCs were suppressed greater than or equal to 90% and ventricular tachycardia was eliminated in 11 of the 12 patients (p less than 0.01). The effectiveness of propafenone for treatment of VPCs was confirmed during the double-blind trial (p less than 0.05 vs double-blind placebo) and during treatment for 6 months (p less than 0.05 vs initial single-blind placebo). Propafenone prolonged the PR interval by 16% (p less than 0.01 vs single-blind placebo) and the QRS interval by 18% (p less than 0.001). Left ventricular systolic performance decreased as assessed by 2-dimensional echocardiography (p less than 0.01 vs single-blind placebo). Propafenone increased serum digoxin levels in 5 of 5 patients (mean increase of 83%). Side effects included exacerbation of congestive heart failure (1 patient) and conduction abnormalities (2 patients). Thus, propafenone is effective for treatment of total and repetitive VPCs. Although generally well tolerated, the drug reduces left ventricular systolic function and atrioventricular conduction and increases serum digoxin levels.