The pharmacokinetic and pharmacodynamic interactions between digoxin and propafenone were investigated in 10 hospitalized patients with heart disease and cardiac arrhythmias. During steady state (0.25 mg/day) the glycoside was combined with 600 mg of propafenone daily for 1 week. The mean\pm SD serum digoxin concentration (SDC) was 0.97\pm 0.29 ng/ml before and 1.54\pm 0.65 ng/ml (p< 0.003) during propafenone administration. Propafenone induced a mean decrease in 31.1 and 31.7% in total and renal digoxin clearances, respectively. The increase in SDCs was accompanied by a decrease in heart rate (HR) and shortening of QT c (QT interval corrected for HR). In patients receiving digoxin and propafenone simultaneously, the SDCs should be monitored and the digoxin dose reduced if there is evidence of toxicity.