Plasma levels of atrial natriuretic peptide (ANP), angiotensin II, aldosterone, and catecholamines were followed for 1 month and then for 4 to 6 months in 55 patients with acute myocardial infarction. Plasma hormones were highest within the first 24 hours after the onset of infarction but normalized during the first few days in patients without heart failure. In patients with symptoms of heart failure, angiotensin II and norepinephrine remained elevated for 1 month and ANP remained elevated for 4 to 6 months. During head-up tilt, angiotensin II and norepinephrine increased most in patients with overt heart failure. Among patients with a first myocardial infarction, a positive correlation was found between infarct size and ANP, angiotensin II, and norepinephrine on day 5 to 7 and between infarct size and angiotensin II during head-up tilt at 1 month, and between infarct size and ANP at 1 month. A similar relationship was found when only patients without heart failure were studied. It is concluded that sustained neurohormonal activation after myocardial infarction mainly occurs in patients with clinical heart failure but is related to the magnitude of myocardial damage, even in patients without heart failure. Measurement of neurohormones during head-up tilt may be an additive assessment for the detection of neurohormonal activation.