This study reports the effects of the new beta 1 adrenoceptor partial agonist, xamoterol, on neuroendocrine activity after acute myocardial infarction (AMI). Fifty-one consecutive patients with AMI were randomized to treatment with xamoterol, 200 mg twice a day, or placebo; patients were also stratified as to whether or not diuretic therapy was given for left ventricular dysfunction. Noradrenaline, plasma renin activity (PRA), and atrial natriuretic factor (ANF) were measured over a 10-day period. Noradrenaline concentrations are higher (p less than 0.05) in patients treated with diuretics at the time of admission and fell over the subsequent 10 days (p less than 0.01). Treatment with xamoterol did not affect this noradrenaline response to myocardial infarction. PRA was also significantly higher in the patients treated with diuretics, and there was a nonsignificant trend for xamoterol to blunt the PRA response in these patients. There was no difference in ANF levels between those patients who were treated with diuretics and those who were not; xamoterol did not affect ANF. Thus xamoterol does not further elevate noradrenaline levels as do conventional beta blockers, and it does not activate the renin-angiotensin system as do potent nonselective beta agonists. Furthermore, xamoterol does not increase ANF levels, probably because it is not negatively inotropic. We conclude that xamoterol does not cause deleterious neuroendocrine changes in patients with AMI even in those treated for heart failure.