Nineteen patients with chronic heart failure participated in a double blind crossover trial of captopril and prazosin--two drugs with differing neuroendocrine effects--to determine whether neuroendocrine changes could explain clinical and haemodynamic responses to treatment. Patients were assessed before and after acute and long term (four weeks') treatment with each drug given in random order. Sixteen patients completed the study. During captopril haemodynamic improvement was maintained by inhibition of the renin-angiotensin system. Breathlessness was relieved in 15 patients and exercise capacity increased. During prazosin a reduction in systemic vascular resistance was maintained, but plasma renin activity and aldosterone and noradrenaline concentrations increased, fluid retention developed, and clinical benefit did not occur. These results suggest that clinical and haemodynamic responses to long term vasodilator treatment for chronic heart failure are related to neuroendocrine changes. In patients with chronic heart failure inhibition of the renin-angiotensin system results in clinical benefit, whereas inhibition of the alpha adrenergic system does not.