In this study, the safety and efficacy of long-term therapy with disopyramide phosphate were evaluated in 40 patients with documented, recurrent, symptomatic tachyarrhythmias. Twenty-one (53%) of the patients had organic heart disease, and nine of these patients had compensated congestive heart failure. The tachyarrhythmias which were treated were paroxysmal supraventricular tachycardia (21 patients), paroxysmal atrial fibrillation (six patients), and paroxysmal ventricular tachycardia (13 patients). In each patient there was evidence, from continuous ECG monitoring or electrophysiologic testing, that disopyramide would be effective therapy, and each patient was able to tolerate disopyramide (no side effects or tolerable side effects) during an initial trial period of 1 to 2 weeks. Dosages of disopyramide were 400 to 1600 mg/day (994 ± 320 mm/day). During long-term therapy, side effects were reported by 28 (70%) of the patients. The side effects were usually anticholinergic, and were usually a continuation of side effects noted during the initial trial period. None of the patients had idiosyncratic reactions to disopyramide. Most of the patients found side effects to be tolerable; however, in seven patients it was necessary to discontinue disopyramide after 1 to 8 (6 ± 3) months. Actuarial incidence of intolerable side effects was 21 ± 7% at 12 months. Nine (22%) of the 40 patients had symptomatic recurrences of tachyarrhythmia after 3 to 32 (15 ± 9) months of therapy. Actuarial incidence of drug ineffectiveness was 32 ± 10% at 24 months. Disopyramide was both effective and tolerated in 24 (60%) of the patients, who were followed for 2 to 64 (23 ± 16) months. In conclusion, it is feasible to use oral disopyramide phosphate as long-term therapy for patients with symptomatic tachyarrhythmias. Anticholinergic side effects, although common, are usually tolerated.