The effect on heart rate variability of adding digoxin to a diuretic and ACE inhibitor was studied in patients with chronic stable cardiac failure. Digoxin was found to increase heart rate variability, especially those measures of heart rate variability thought to represent parasympathetic activity. The withdrawal of digoxin led to a decrease in heart rate variability to pre-treatment levels. Whilst digoxin in standard doses does not alter prognosis in chronic cardiac failure, it does have potentially beneficial neurohumoral effects. If the increase in heart rate variability, which represents beneficial neurohumoral modulation, can be divorced from the potentially detrimental effects, perhaps by using smaller doses, then there may be a role for digoxin in the treatment of chronic cardiac failure.