Neurohumoral activation in acute myocardial infarction (AMI) may reflect the degree of hemodynamic compromise, contribute to the progression of heart failure and augment to the risk of serious ventricular arrhythmias. Consequently, assessment of neurohumoral variables may provide an index of prognostic value in AMI. Plasma levels of atrial natriuretic factor (ANF), norepinephrine and epinephrine were determined in 145 patients on day 3 after AMI. During the 360-day follow-up period 17 patients died. In univariate analysis, all 3 neurohormones were significantly related to 1-year mortality rates (ANF, p < 0.001; norepinephrine, p = 0.009; epinephrine, p = 0.048). After correction for age, sex, anamnestic, biochemical and clinical variables including signs of clinical heart failure in a multivariate model, ANF remained independently related to mortality. The association between plasma norepinephrine and survival failed to reach statistical significance after introduction of clinical heart failure in the model. Comparison of patients subdivided according to median hormone levels (ANF, 30.3 pmol/liter; norepinephrine, 2.29 nmol/liter) demonstrated a significantly increased mortality rate in patients with elevated ANF (p < 0.001), but not elevated norepinephrine levels. These results suggest that early plasma ANF levels are related to survival in patients with AMI, independently of signs of clinical heart failure.