Functional mitral regurgitation plays a major role in determining the therapeutic response to vasodilators in patients with severe congestive heart failure. Its role in the response to inotropic therapy has not been studied in these patients. Ten patients with stage 3 or 4 congestive heart failure (New York Heart Association class) and secondary mitral regurgitation were studied before and during intravenous administration of dobutamine (mean dose, 7.4 microgram/kg/min). Hemodynamic measurements were obtained invasively. Echo and Doppler cardiography were used to determine cardiac volumes. Mitral regurgitation was calculated as the difference between total stroke volume by echo and forward stroke volume by Doppler. Mitral regurgitation area was calculated from a modified hemodynamic formula. Dobutamine caused a marked rise in mean forward stroke volume (43 to 61 ml), with a decrease in mitral regurgitation volume from 20 to 10 ml/beat and a drop in pulmonary capillary wedge pressure from 21 to 13 mm Hg. Since the pressure gradient between the left ventricle and atrium increased significantly during dobutamine therapy, only a marked decrease in the orifice of regurgitation could explain the changes in regurgitant volume. Indeed, the end-diastolic volume decreased from 254 to 234 ml and the orifice of mitral regurgitation was reduced from 0.25 to 0.12 cm2.