The purpose of this investigation was to evaluate the effect of digoxin on aerobic performance in mildly symptomatic patients with congestive heart failure and sinus rhythm. Ten patients (8 men and 2 women) with idiopathic dilated cardiomyopathy (ejection fraction 17 to 33%, mean 27 +/- 4%) who were stable and mildly symptomatic with maintenance digoxin and diuretic therapy were studied. All patients underwent maximal symptom-limited ergometer exercise with analysis of respiratory gases during maintenance digoxin therapy, 4 weeks after digoxin withdrawal, and 4 weeks after digoxin readministration. Exercise capacity was assessed by peak oxygen uptake and anaerobic threshold. Serum digoxin concentration was 1.0 to 1.8 (mean 1.3 +/- 0.2) ng/ml during digoxin therapy, and less than the detectable level after digoxin withdrawal. No patients showed clinical deterioration after digoxin withdrawal. Peak oxygen uptake after digoxin withdrawal (23.7 +/- 3.0 ml/kg/min) did not differ significantly from that during maintenance digoxin therapy (23.8 +/- 2.5 ml/kg/min) or after digoxin readministration (24.1 +/- 2.9 ml/kg/min). The anaerobic threshold after digoxin withdrawal (14.9 +/- 2.5 ml/kg/min) did not differ significantly from that during maintenance digoxin therapy (15.0 +/- 2.1 ml/kg/min) or after digoxin readministration (14.9 +/- 2.2 ml/kg/min). No differences in heart rate and diastolic blood pressure were observed during exercise, but systolic blood pressure during exercise was significantly higher with digoxin therapy (p < 0.05). These results suggest that digoxin has no effect on aerobic performance in mildly symptomatic patients with idiopathic dilated cardiomyopathy and sinus rhythm.