To evaluate the importance of oral maintenance digoxin therapy in chronic congestive heart failure (CHF), 24 patients in sinus rhythm on maintenance digoxin for documented CHF were studied prospectively on and off the drug. The average duration of therapy was 39 months (range 2 to 180). All 24 patients had documented coronary artery disease (CAD): 22 were in New York Heart Association functional class III and 2 in class II. Twenty-one patients (88%) were receiving diuretic or vasodilator therapy, or both, before digoxin discontinuance. At 1 month off digoxin and with no increase in doses of other medications excepting minor increases in antianginal therapy in 2 patients, no difference was observed in the group as a whole in symptoms, resting heart rate, arterial blood pressure, physical findings, weight, cardiothoracic ratio, radiographic signs of pulmonary congestion, radionuclide left ventricular ejection fraction (LVEF), duration of symptom-limited treadmill exercise (14 patients), or CHF score, compared with evaluation during maintenance digoxin therapy. Similar results were obtained in a subgroup of 9 patients with a resting LVEF less than 0.35 (0.27 +/- 0.02; mean +/- standard error of the mean). Six patients had a decrease and 5 patients an increase in LVEF of greater than or equal to 0.05 units after cessation of digoxin. Off digoxin, the CHF score increased by only 1 point in 2 patients, but also decreased in 2 patients. Thus, in this study population comprised of patients with CAD with documented CHF, most of whom were receiving diuretics or vasodilators, or both, digoxin withdrawal had no adverse clinical or hemodynamic effects.