To determine whether an acute fall in atrial pressure decreases the secretion of atrial natriuretic peptide in man, changes in the plasma levels of this peptide were studied after catheter balloon valvuloplasty of the mitral valve. Ten patients with severe mitral stenosis were included in the study. The valvuloplasty resulted in an immediate reduction in left atrial pressure and an increase in the mitral valve area. Decreases in right atrial pressure were inconsistent and less significant. Plasma atrial natriuretic peptide levels, which were elevated before the valvuloplasty, decreased significantly in all 10 patients at 15 minutes after the valvuloplasty and reached lower plateaus at 30, 45, and 60 minutes after the procedure. In the seven patients studied for a longer period, both plasma atrial natriuretic peptide levels and the left atrial pressure remained reduced 24 hours after the valvuloplasty. Plasma atrial natriuretic peptide levels before and 30 to 60 minutes after the valvuloplasty were positively correlated to simultaneously determined left and right atrial pressures. These results indicate that atrial stretch caused by increased atrial pressure is an important stimulus for atrial natriuretic peptide release in man. "De-stretching" of the myocytes of the atria results in rapid inhibition of atrial natriuretic peptide secretion.