Aim: The study was designed to assess temporal changes in atrial natriuretic peptide (ANP) and endothelin-1 (ET) concentrations in patients hospitalized for acute myocardial infarction (AMI) and their relationships to cardiac performance determined by radionuclide ventriculography. Patients and Methods: 20 patients with first AMI were studied. Blood samples were drawn within the first 4–18 h, after 18–24 h, and on days 2, 3 and 6. Plasma concentrations of ANP and ET were measured in blood samples taken simultaneously. Radionuclide ventriculography was performed on the day of discharge to determine left-ventricular ejection fraction (LVEF), left-ventricular end-diastolic volume index, end-systolic volume index and left-ventricular stroke volume index. Results: Median concentrations of ET decreased from 2.15 pmol/l on admission to 1.45 pmol/l at discharge (32%, p < 0.001). Median ANP rose from 29 to 79 pg/ml (172%, p < 0.001). The increment in ANP and the decrease in ET concentrations from admission to discharge was inversely correlated (r = –0.81, p < 0.005). ANP was inversely correlated to LVEF (r = –0.82, p < 0.001) and to the end-systolic volume index at discharge (r = –0.73, p < 0.003). Conclusion: Dynamic and inverse fluctuations in ET and ANP occur within the 1st week of AMI. The magnitude of endocrine activation in the ANP-ET system seems to reflect an impairment in the left-ventricular systolic performance.