The hemodynamic response to afterload reduction by sodium nitroprusside was assessed in 5 patients with mitral regurgitation and in 7 with aortic regurgitation. The drug significantly lowered left ventricular systolic pressure, end-diastolic pressure and end-diastolic volume. In patients with mitral regurgitation, significant decreases in regurgitant volume (74 +/- 10 to 44 +/- 7 ml) and regurgitant fraction (60 +/- 4 to 41 +/- 5%) were associated with substantial increases in cardiac output (4.18 +/- 1.18 to 5.43 +/- 1.18 L/min) and forward stroke volume (49 +/- 10 to 64 +/- 9 ml). In patients with aortic regurgitation, vasodilator therapy was effective in increasing forward output only in 2 patients who had an initially elevated end-diastolic pressure which was reduced only to levels slightly above normal with nitroprusside. In patients with a lower level of end-diastolic pressure, further reduction in the filling pressure resulted in no benefit or rather a fall in forward stroke volume, despite a significant increase in pump function (ejection fraction being augmented from 55 +/- 4 to 61 +/- 5%). Experiments in dogs confirmed that nitroprusside reduced the amount of mitral regurgitation by virtue of diminishing the regurgitant orifice size, as a result of the reduction in size of the left heart chamber. These observations also support the concept that it is ultimately important to maintain filling pressure at an optimal level during administration of a vasodilating agent, otherwise effects due to afterload reduction tend to be offset.