Malignant ventricular arrhythmias often occur in patients with left ventricular (LV) dysfunction. Antiarrhythmic drugs may further impair LV function in these patients. Mexiletine, a lidocaine congener, is an effective antiarrhythmic drug, but when administered orally, its effect on LV and right ventricular (RV) function is unknown. To determine the hemodynamic effects of mexiletine, LV and RV ejection fraction (EF) were measured by radionuclide ventriculography in 10 patients with LV dysfunction (LVEF less than 50%). Symptom-limited exercise tests were also performed. Patients were studied before and during therapy with oral mexiletine. There was no significant change in LVEF (28% vs 27%) or RVEF (46% vs 41%). Also, heart rate at rest, exercise duration and peak heart rate during exercise were unchanged. Thus, in patients with LV dysfunction, oral mexiletine does not significantly affect LV or RV function.