Clinical evaluation of oral milrinone in moderate to severe heart failure has demonstrated pronounced beneficial effects. These effects are achieved through increased cardiac index and exercise tolerance, and reduced ventricular filling pressure and systemic vascular resistance. In a double-blind, multicentre study of 230 patients with moderate to severe failure receiving diuretic therapy, treatment with milrinone or digoxin significantly improved exercise capacity. No additional benefit was obtained using combined treatment with the two drugs. A sub-study of 60 patients showed that milrinone produced a significantly higher peak oxygen consumption during treadmill exercise compared with placebo, and approached a significant improvement over digoxin. Milrinone and digoxin favourably influenced symptoms and quality of life measures, but NYHA class was unaltered. Both treatments were well tolerated, alone or combined. A similar study of 155 patients showed comparable results, with no evidence of tolerance development during chronic (3-month) treatment. Survival during the 3-month studies showed a strong correlation with baseline resting left ventricular ejection fraction and was independent of treatment. Neither treatment adversely affected survival. These studies show that milrinone is a well-tolerated and effective oral agent that provides clinical benefits beyond those obtained with diuretics alone in moderate to severe heart failure.