Tocainide, an oral analog of lidocaine, was evaluated as a long-term antiarrhythmic agent in 21 patients with symptomatic complex ventricular ectopic activity (10 with hemodynamically significant ventricular tachycardia) refractory to currently available antiarrhythmics singly, and in combination for periods of 3 days to 35 months (mean 13.6 months). Tocainide appeared to be an effective and safe agent for the control of these refractory symptomatic ventricular arrhythmias in 14 of the 21 patients (66%). Minor central nervous system and gastrointestinal side effects were present in most of the patients, usually early on in therapy, and only precluded long-term use in 2 patients. Furthermore, lidocaine responsiveness was a good predictor of tocainide effectiveness in this group of patients. Tocainide precipitated atrioventricular (A-V) block in one patient with pre-existing A-V nodal disease; two patients developed a skin rash while on tocainide therapy. These two patients had previously developed lupus-like syndromes and skin rashes while on procainamide. The ANA titers had been falling in these two patients while on tocainide, and in one of these patients with true systemic lupus erythematosus, rechallenge with tocainide failed to produce skin rash. Tocainide's long plasma half-life and high oral bioavailability permit an 8-h regime. We conclude that tocainide is an effective, safe antiarrhythmic agent with tolerable side effects.