Angiographic results in patients with mitral regurgitation suggest that up to 50% of the regurgitant volume occurs during the preejection period. This contrasts markedly with the electromagnetic measurements of mitral regurgitant flow in anesthetized dogs, which suggest that only 5% of mitral regurgitant flow occurs during the preejection period. Therefore, we used two-dimensional and Doppler echocardiography to quantify mitral regurgitation during aortic ejection and in the preejection and postejection periods in eight patients with severe heart failure. Mitral regurgitant volume (RV) was calculated as the difference between total stroke volume (by two-dimensional echocardiography) and forward aortic flow (by pulsed Doppler). Regurgitant velocity (V) and time (RT) were measured by continuous-wave Doppler, and the mean regurgitant area (RAm) was calculated from the RT and mean regurgitant velocity (Vm): RAm - (RV/RT)/Vm. As a first approximation, the RA was assumed to be constant during systole, and the regurgitant volume during aortic ejection and during the preejection and postejection periods was calculated from: RVi = (Vmi) (RTi) (TAm), where Ti represents the duration of the appropriate period. Percentages of total regurgitant volume occurring during the preejection, ejection, and postejection periods were 13 ± 4%, 79 ± 5%, and 8 ± 5%. respectively. Thus, in contrast to previously reported angiographic studies, mitral regurgitation occurs predominantly during the aortic ejection period. These results were not substantially changed by assuming a 20% reduction in effective regurgitant orifice area between the preejection and ejection periods and are consistent with data from chronically instrumented dogs with mitral regurgitation. Furthermore, our findings are supported by a computer model of the central circulation that was modified to include an incompetent mitral valve. The model offers significant insight into the physiologic mechanisms governing phasic changes in mitral regurgitant volume.