Heart transplantation is currently the most effective therapy for patients with severe heart failure due to dilated cardiomyopathy, although long-term survival without transplantation has been described in a few patients. We have identified five patients with severe heart failure who experienced a significant clinical and hemodynamic improvement while they were waiting for heart transplantation. At initial assessment, all five patients were symptom-class 4; left ventricular end-diastolic pressure was 33 +/- 4 mm Hg, left ventricular ejection fraction was 0.20 +/- 0.01, left ventricular end-systolic volume was 130 +/- 3 ml/min/m2, and cardiac index was 2.1 +/- 0.1 L/min/m2. These patients showed a marked improvement at two to ten months after initial assessment, while they were waiting for a donor heart. After a follow-up of 10 to 31 months (mean follow-up, 20 months), the five patients were still alive and their clinical and hemodynamic condition remained stable. On the contrary, survival was less than 15 percent at six months for the remaining patients with indications for heart transplantation but in whom transplant could not be performed because of the existence of contraindications or lack of donors; all these patients were dead at 18 months after initial assessment. The five patients who developed spontaneous favorable outcome showed a trend to have higher serum sodium values, shorter symptomatic history, lesser need for intravenous inotropic support, and better response to medical therapy than the other patients. Our findings suggest that some patients with transplants could have experienced a sustained and spontaneous clinical and hemodynamic recovery with medical therapy alone, although it seems currently difficult to identify patients with this favorable outcome.