516 patients with New York Heart Association class III and IV heart failure despite treatment with diuretics and angiotensin converting enzyme inhibitors were randomised in a double-blind between-group comparison to xamoterol 200 mg (352) or placebo (164) twice daily for 13 weeks. There was no difference between the treatments in loss of clinical signs. Visual analogue scale and Likert scores indicated that breathlessness was less severe with xamoterol, but there was no difference in exercise duration or total work done. Xamoterol reduced maximum exercise heart rate and systolic blood pressure, did not affect the number of ventricular premature beats after exercise, showed no arrhythmogenic activity, and had variable (agonist and antagonist) effects on 24 h heart rate. On intention-to-treat analysis 32 (9.1%) patients in the xamoterol group and 6 (3.7%) patients in the placebo group died within 100 days of randomisation (p = 0.02).