The effect of flecainide, 200 mg twice daily for 5 days, on steady-state plasma digoxin levels was determined in 15 healthy male subjects who received 0.25 mg of digoxin per day. The predose mean plasma digoxin level before flecainide administration on days 9 and 10 was 0.46 ng/ml, compared with 0.57 ng/ml on day 13 (p less than 0.05) and 0.49 ng/ml on day 15 (difference not significant [NS]) when flecainide was given concurrently with digoxin. The 6-hour postdose mean level for days 9 and 10 was 0.58 ng/ml, compared with mean levels of 0.62 ng/ml on day 13 (NS) and 0.65 ng/ml on day 15 (p less than 0.05). On average, predose and 6-hour postdose digoxin levels increased by 24 +/- 35% and 13 +/- 19%, respectively, during co-administration. A significant prolongation of the electrocardiographic PR interval in 6 of 15 subjects was noted on the combined drug dosage. This reverted to normal after cessation of drug administration. Vital signs showed no significant clinical change during the course of the study. Ten other healthy male subjects were given propranolol, 80 mg 3 times daily, or flecainide, 200 mg twice daily, alone or in combination. Effects on vital signs, exercise heart rate, electrocardiographic interval, M-mode indexes of ventricular function and plasma drug levels were monitored to determine effects of the study drugs when given separately or concurrently. Both drugs caused a decrease in blood pressure, with the systolic pressure affected more than the diastolic; the effects of propranolol and flecainide were additive.(ABSTRACT TRUNCATED AT 250 WORDS)