The effects of amiodarone on the pharmacokinetic and electrophysiologic properties of procainamide were examined in eight patients treated for recurrent ventricular arrhythmias who received intravenous procainamide, 6 to 15 mg/kg, at control and after 1 to 2 weeks of oral amiodarone treatment. Compared with control, procainamide plasma clearance decreased from 0.43 +/- 0.12 L/kg-hr to 0.33 +/- 0.12 L/kg-hr (P less than 0.01), plasma elimination half-life increased from 3.77 +/- 0.64 hours to 5.21 +/- 0.42 hours (P less than 0.01), and volume of distribution was unchanged from 2.31 +/- 0.74 L/kg to 2.47 +/- 0.90 L/kg during amiodarone treatment. As single agents, intravenous procainamide and oral amiodarone produced equivalent increases in QRS duration, rate-corrected QT interval, right ventricular effective refractory period, and cycle length of induced ventricular tachycardia. After the addition of intravenous procainamide to amiodarone the QRS duration, rate-corrected QT interval, and, in six of eight patients, ventricular tachycardia cycle length were significantly increased compared with control or either drug alone, suggesting additive electrophysiologic effect. However, acceleration of induced ventricular tachycardia occurred in one patient with combined treatment, suggesting a potential for adverse electrophysiologic interactions. These findings indicate that amiodarone has pharmacokinetic and electrophysiologic interactions with procainamide and suggest that the intravenous dose of procainamide be reduced by 20% to 30% during concurrent drug administration.