The effect of oral mexiletine therapy on ventricular arrhythmias was evaluated in 58 patients in whom conventional drugs had been unsuccessful. Mean daily dose of mexiletine was 652 mg (range 250 to 1,500) and mean duration of therapy was 14.4 months (range 0.1 to 34.4). Mexiletine was associated with a decrease of 52% in total premature ventricular complexes in 24 hours compared with control (6,841 +/- 1,053 [SEM] versus 3,248 +/- 734, p less than 0.005) and 19 patients (36.5%) had a greater than 83% decrease in ventricular ectopic rhythm. The drug was discontinued in 6 of these 19 patients because 5 of them (26%) experienced side effects after a mean period of 29.6 weeks (range 0.83 to 63.2) and sudden death occurred in 1 patient (5%); this indicates effective suppression of ventricular ectopic rhythm without significant side effects in 13 (25%) of 52 patients during long-term therapy. Adjustment of drug dosage to achieve therapeutic blood levels resulted in an efficacy on ventricular ectopic rhythm similar to that obtained with the maximal tolerated dose. There was no correlation between drug dose and therapeutic effectiveness. Mexiletine was associated with a 48% decrease in episodes of ventricular tachycardia (345.5 versus 179.3/24 h) and 5 of 10 patients with a history of cardiac arrest remained free of symptomatic ventricular tachyarrhythmias for 14.8 months (range 3.7 to 24.3).(ABSTRACT TRUNCATED AT 250 WORDS)