Pulsed and continuous wave Doppler velocity measurements are routinely used in clinical practice to assess severity of stenotic and regurgitant valves or to estimate intracavitary pressures. However, this method only evaluates the convective component of the pressure gradient (based on the velocity measurements) and neglects the contribution of inertial forces that can be important, in particular for flow across nonstenotic valves. Digital processing of color Doppler ultrasound data was used to noninvasively estimate both the convective and inertial components of the transmitral pressure difference. Simultaneous pressure and velocity measurements were obtained in six anesthetized open-chest dogs. The instantaneous diastolic transmitral pressure difference is computed from the M mode spatiotemporal velocity distribution using the unsteady flow form of the Bernoulli equation. The inclusion of the inertial forces ([delta PI]max = 0.90 +/- 0.30 mmHg) in the noninvasive pressure difference calculation significantly increased the correlation with catheter-based measurement (r = 0.15 +/- 0.23 vs. 0.85 +/- 0.08; P < 0.0001) and also allowed an accurate approximation of the peak early filling pressure difference ([delta PC+I]max = 0.95[delta Pcath]max + 0.07, r = 0.92, P < 0.001, error: epsilon C+I ([delta PC+I]max-[delta Pcath]max) = 0.01 +/- 0.24 mmHg, N = 90]. Noninvasive estimation of left ventricular filling pressure differences using this technique will improve the understanding of diastolic filling and function of the heart.