Antiarrhythmic properties of N-acetylprocainamide (NAPA), an active metabolite of procainamide, were studied in 12 patients with coronary artery disease who presented with cardiac arrest or documented sustained ventricular tachycardia (VT). Programmed electrical stimulation (PES) studies were performed in 10 men and 2 women, aged 52 to 80 years (mean 63), who had a left ventricular ejection fraction of 16 to 69% (mean 33). All patients tested had inducible VT provoked by PES without antiarrhythmic therapy. Patients were then tested with procainamide, 1,000 mg administered intravenously. VT could be provoked after procainamide treatment in 8 of 10 patients. Twenty-four to 36 hours later NAPA was administered, 18 mg/kg body weight intravenously, and PES was performed after 20 minutes. NAPA did not significantly change heart rate, mean arterial blood pressure, electrocardiographic intervals and AH or HV conduction times. The QT interval lengthened, but not significantly. The mean serum NAPA levels were 15.7 +/- 4 micrograms/ml in the group protected by NAPA and 16.2 +/- 4 micrograms/ml in the group not protected by NAPA. Five patients were discharged with NAPA therapy, 1.5 g orally every 8 hours. Two patients have been maintained with chronic NAPA therapy (10 +/- 3 months), and 2 patients had breakthrough VT on follow-up Holter monitoring and alternative therapy was given. One patient died while taking oral therapy. NAPA demonstrates antiarrhythmic efficacy in preventing induction of VT by PES in a high-risk group of patients. During chronic oral therapy in some patients, NAPA appears to be well tolerated, with antiarrhythmic efficacy that may be enhanced with further upward dose titration.