To study the physical and physiological determinants of transmitral and pulmonary venous flow, a lumped-parameter model of the cardiovascular system has been created, modeling the instantaneous pressure, volume, and influx/efflux of the pulmonary veins, left atrium and ventricle, systemic arteries and veins. right atrium and ventricle, and pulmonary arteries. Initial validation has been obtained by direct comparison with transesophageal echocardiographic recordings of mitral and pulmonary venous velocity for the following clinical situations: normal diastolic function, delayed ventricular relaxation, restrictive filling due to severe systolic dysfunction, severe mitral regurgitation before and after valve repair surgery, and premature atrial contraction occurring during ventricular systole. Sensitivity analysis has been performed with a Jacobian matrix, representing the proportional change in a group of output indexes (yi) in response to isolated changes in input parameters (xj), [(delta yi/yi)/ ([delta xj/xj)], demonstrating the complementary nature of mitral and pulmonary venous A-wave velocity for predicting ventricular stiffness and atrial systolic function. This unified numerical-experimental programming environment should facilitate model refinement and physiological data exploration, in particular guiding more accurate interpretations of Doppler echocardiographic data.