Acute mitral regurgitation (MR) was produced in 12 dogs by closed chest partial valvulectomy and the relative contributions of MR pressure gradient (MRG), the time for regurgitant flow (VSI), and the MR orifice area (MRA) to mitral regurgitant volume (MRV) assessed. Aortic and left atrial pressures, biplane left ventricular (LV) angiography, forward flow and mitral regurgitant flow (MRF) were measured following MR induction and following augmentation of left ventricular end-diastolic volume (EDV), increased aortic resistance (angiotensin), and in the presence of increased ventricular contractility (calcium or epinephrine). Mitral regurgitation orifice area was determined by calculation and the diameters of the mitral anulus and subvalvular areas measured angiographically. Angiotensin and volume infusion induced a substantial increase in MRF which was largely dependent on an increase in MRA but not MRG, while augmentation of contractility decreased MRF accompanied by a decrease in MRA, relatively independent of MRG. Left ventricular size and shape are major determinants of MRA and resultant MRF in acute mitral regurgitation. These findings may help to explain the effects of such factors as ventricular loading and volume on the clinical course of mitral regurgitation in man.