To clarify the direct contribution of the left atrial pressure to secretion of human atrial natriuretic peptide (hANP), we have attempted to study the relations between plasma hANP levels, neurohumoral factors, and hemodynamic changes in 13 patients with mitral stenosis undergoing percutaneous transvenous mitral commissurotomy (PTMC). After PTMC, the left atrial pressure fell from 14.7±1.9 (mean±SEM) to 6.5±0.7 mm Hg in all patients studied (p< 0.0005), whereas there were no remarkable changes in either the right atrial pressure, mean arterial pressure, or heart rate. Plasma immunoreactive hANP levels obtained from the pulmonary artery decreased from 278±51 to 137±31 pg/ml after PTMC (p< 0.0005). There was a significant correlation between the decrement of hANP levels and that of left atrial pressure (r= 0.72,p< 0.005). Neither plasma renin activity nor norepinephrine levels changed. In contrast, plasma aldosterone concentrations significantly increased from 11.3± 1.5 to 16.4±2.7 pg/ml after PTMC (p< 0.01), although there was no causal relation between plasma concentrations of aldosterone and hANP. The present result with PTMC-induced rapid fall of the left atrial pressure with a concomitant reduction in hANP secretion strongly suggests the importance of the left atrial pressure on hANP secretion in humans.