Background-Functional mitral regurgitation (MR) is common in patients with heart failure and left ventricular (LV) dysfunction, and its severity may vary over time, depending primarily on the loading conditions. Because dynamic changes in the severity of functional MR may affect forward stroke volume, we hypothesized that exercise-induced changes in MR severity influence the stroke volume response of patients with LV dysfunction to exercise, and hence their exercise capacity. Methods and Results-Heart failure patients (nϭ25; mean age 53Ϯ12 years) with LV dysfunction underwent dynamic bicycle exercise at steady-state levels of 30%, 60%, and 90% of predetermined peak V O 2 . During each exercise level, right heart pressures, cardiac output, V O 2 , and MR severity were measured simultaneously. During exercise, MR severity, as evaluated by the ratio of MR jet over left atrium area, increased from 15Ϯ8% to 33Ϯ15%. Peak V O 2 , exercise-induced changes in stroke volume, and those in capillary wedge pressure correlated with the changes in MR (rϭϪ0.55, Ϫ0.87, and 0.62, respectively, PϽ0.01). The changes in MR severity also correlated with those in end-diastolic (rϭϪ0.75, PϽ0.01) and end-systolic (rϭϪ0.72, PϽ0.01) sphericity indexes and those in the coaptation distance (rϭ0.86, PϽ0.01). Conclusions-Our data indicate that in patients with LV dysfunction, exercise-induced changes in MR severity limit the stroke volume adaptation during exercise and therefore contribute to limitation of exercise capacity.