Acute antiarrhythmic drug testing with disopyramide was accomplished in 25 patients with frequent ventricular premature depolarization (VPD). Systolic time intervals (STI) were used to assess left ventricular performance. Eighteen patients responded after a loading oral dose of 300 mg disopyramide with 80% or greater reduction in VPD and abolition of advanced grades. Mean onset of drug action was 93 min and the mean plasma level at 2 h was 3.4 microgram /ml. During maintenance therapy 2 of the 18 patients had a relapse, In 2 others, initially protected, VPD recurred during both exercise and psychological stress testing. STI showed increments in pre-ejection period (PEP) and in PEP/ejection time ratio at peak concentrations of plasma disopyramide. Acute tests repeated with placebo in a single-blind fashion in responding patients failed to significantly reduce VPD frequency or grade. Side effects consisted of anticholinergic actions of disopyramide. In 3 patients aggravation of heart failure compelled discontinuation of disopyramide which then remitted.