The effects of orally administered propafenone on ejection fraction (EF) determined by radionuclide angiography were studied in 2 groups of patients receiving different dosing regimens. Fourteen group A patients had no clinical evidence of left ventricular (LV) dysfunction and were not receiving digoxin therapy. In this group a mean daily dosage of 879 mg resulted in a decrease in resting LVEF from 52 +/- 9% to 48 +/- 11% (p less than 0.05). Eight group B patients had clinical radionuclide evidence of LV dysfunction and were receiving digoxin therapy. In this group, a daily dosage of propafenone of 600 mg/day resulted in no significant change in LVEF. No clinically significant effects on cardiac compensation were evident in either group. These data suggest a negative inotropic effect that is either related to propafenone dosage or at least partially attenuated by digoxin therapy. Further studies are necessary to define precisely the effects of propafenone on LV function.