We evaluated the efficacy of a single oral dose of procainamide to terminate paroxysmal tachycardia, when procainamide was taken shortly after onset of tachycardia, a regimen we have termed 'periodic procainamide'. In 12 patients (mean age 15 years) with non-life-threatening tachycardia (orthodromic reciprocating tachycardia, 8/12; ventricular tachycardia, 3/12; atrial flutter, 1/12) in whom intravenously administered procainamide (15 mg/kg at 1 mg/kg/min) terminated tachycardia, efficacy of a single oral dose of procainamide (25 mg/kg) to terminate tachycardia was tested during electrophysiologic study. After oral administration of procainamide, tachycardia was terminated and could not be reinitiated in 11 of 12 patients (9/12<75 min, 2/12>120 min after administration). Time to tachycardia termination approximately coincided with the time of peak serum concentration of procainamide after the sigle oral dose. Delayed response or failure of procainamide to terminate tachycardia was associated with delayed and diminished peak serum procainamide concentration. After evaluation, 10 responders were instructed to take a single dose of procainamide when tachycardia occurred. During a mean follow-up of 9 months (range 2 to 17) seven of 10 patients had an opportunity to use period procainamide on one to more than 100 occasions; four of 10 patients have not had recurrence of tachycardia. Tachycardia was successfully terminated in six of seven patients using the periodic regimen and could not be terminated on the first out-of-hospital use in one of seven patients. Success of periodic procainamide was predicted during evaluation by rapid termination of tachycardia after oral administration.