The unifying hypothesis of this investigation is that the progressive increase in regurgitant volume in patients with long-term MR stimulates activation of the sympathetic nervous system (SNS) as a compensatory mechanism to maintain effective forward output, arterial pressure, and tissue perfusion. This compensatory mechanism affects a decrease in beta AR responsiveness resulting in LV contractile dysfunction. It follows, therefore, that treatment with mitral valve surgery will restore LV contractile function to the extent that SNS activity is diminished and beta AR responsiveness is restored. Preliminary studies in five patients have demonstrated a relationship between regurgitant volume and adenylyl cyclase activity (r=0.86) and contractile function (r=0.75). Similarly, correlatal plasma norepinephrine levels and adenylyl cyclase activity reserved with contractile function (r=0.91 & 0.65). Thus, preliminary data support the hypothesis.