OBJECTIVE--To investigate the relation between plasma concentrations of immunoreactive endothelin and haemodynamic variables before and after percutaneous transvenous balloon dilatation of the mitral valve. DESIGN--Prospective study. SETTING--National cardiovascular centre. PATIENTS--25 patients with mitral stenosis and 26 healthy volunteers. MAIN OUTCOME MEASURES--Plasma concentrations of immunoreactive endothelin were measured in the pulmonary artery, left atrium, ascending aorta, and femoral vein before and after balloon dilatation of the mitral valve. RESULTS--Peripheral venous concentrations (mean (SD)) of endothelin were higher in the patients with mitral stenosis than in the healthy volunteers (1.76 (0.51) v 1.37 (0.45) pg/ml, p < 0.05) and they correlated with the mean left atrial pressure (r = 0.74, p < 0.01). Balloon dilatation of the mitral valve reduced the mean left atrial pressure without changing the mean right atrial pressure, systemic arterial pressure, heart rate, or cardiac index. Concentrations of plasma endothelin in the femoral vein increased from 1.76 (0.51) to 3.39 (2.46) (p < 0.01), 4.82 (2.34) (p < 0.001), and 2.43 (0.52) pg/ml (p < 0.05) at 15 and 30 minutes and 24 hours after the procedure. The concentration of endothelin in the pulmonary artery also increased from 1.85 (0.85) to 4.32 (1.58) pg/ml (p < 0.01) 30 minutes after the dilatation, whereas there were no appreciable changes in endothelin concentration in the left atrium or ascending aorta. CONCLUSIONS--Plasma endothelin concentrations were higher in patients with mitral stenosis than in healthy volunteers and the increase was proportional to left atrial pressure. After balloon dilatation of the mitral valve there was an abrupt rise in endothelin in the femoral vein and pulmonary artery but no change in left atrial or aortic blood samples. These findings suggest that endothelin may be another vasoactive substance involved in congestive heart failure.