Methods for testing long-term efficacy of antiarrhythmic agents are not established. Therefore, an algorithm was developed to assess the response of ventricular premature complexes and ventricular tachycardia to long-term therapy. In 21 patients tocainide, an oral lidocaine analog, was successful in acutely suppressing ventricular premature complexes and ventricular tachycardia. Suppression was assessed with use of both the arrhythmic classification of Lown and Wolf and counts of premature ventricular complexes from 24 hour ambulatory electrocardiographic recordings. After 3 to 10 months of tocainide therapy, 24 hour control recordings were obtained in 18 patients, and administration of tocainide was stopped. With use of recordings obtained 5 and 7 days later to assess variability in the count of ventricular premature complexes, the upper 95 percent confidence limit for variation in number of complexes after arcsin transformation to correct for noncentral distribution was 80 percent. When tocainide was withdrawn, arrhythmias did not reappear in 6 patients but their reappearance in 12 patients indicated a continued requirement for tocainide. Although the decrease in ventricular premature complexes was less than 80 percent in four patients, ventricular tachycardia was effectively suppressed. Four patients had adverse reactions requiring drug withdrawal: a rash (one patient), cervical muscle spasms (one patient) and central nervous system symptoms (two patients). Minor central nervous symptoms persist in six patients. Tocainide did not induce lymphocytotoxicity. It is concluded that testing of long-term antiarrhythmic drugs should include a withdrawal trial to ensure both continued drug requirement and continued drug efficacy. Because of marked variability in ventricular premature complex counts, adequate suppression is best assessed by combining an analysis that considers arrhythmia classification and the nonparametric distribution of data.