Aim of our study was to investigate the pathophysiological role of vasoactive intestinal peptide (VIP) in the neuroendocrine activation occurring in acute myocardial infarction (AMI). Plasma VIP concentration has been assayed in 30 patients with AMI, 22 males and 8 females, aged 41-82 years, without other important diseases. VIP plasma values, assayed on admission to the Coronary Care Unit, within 4-6 hours after the onset of chest pain, everyday for the first week and on day 14, were significantly higher in survivors and in patients aged < 60 years. VIP plasma concentration was not statistically correlated with CPK and CPK-MB. VIP seems to play a pathophysiological role in the neuroendocrine activation occurring in AMI. Low VIP plasma levels are associated with an unfavorable short-term prognosis. Moreover, it appears that VIP secretion is negatively influenced by aging.