To investigate the mechanism in which plasma noradrenaline concentration (pNA) is elevated in heart failure, the effect of balloon mitral valvuloplasty was used as a model of acute manipulation of the left atrial pressure reduction in ten patients with mitral stenosis. Gorlin mitral valve area and pNA were correlated with New York Heart Association functional class and found to have a significant exponential inverse relationship with each other ([pNA, pg/ml] = 198.9 x [mitral valve area, cm2]-0.696; P = 0.003). Elevated pNA could be partially explained by a reduced cardiac index (CI) ([pNA, pg/ml] = 403.4 x [CI, l/min/m2]-0.889; P = 0.027; r = 0.495), especially in severely failed hearts, but not by pulmonary capillary wedge pressure (PCWP). However, the percent changes (% delta) of variables early after balloon valvuloplasty exhibited a paradoxical contrast; % delta pNA showing a clear negative exponential correlation with % delta PCWP ([% delta pNA] = 436.0 x [% delta PCWP + 80]-0.679 - 80; P = 0.021), but not with % delta CI. These results suggest that pNA should be considered an indicator of cardiac functional class in mitral stenosis. PNA is modulated by both cardiac index and pulmonary capillary pressure, but in different ways.