Although recent animal and clinical studies suggest that Doppler-derived indexes may be useful for the characterization of ventricular diastolic behavior, the hemodynamic basis for the preload dependency of these indexes has not previously been fully elucidated. Accordingly, effects of reduction of left atrial load on the pressure-flow velocity relation were characterized in 10 anesthetized, closed-chest dogs during transient inferior vena caval occlusion by means of simultaneously recorded left atrial and left ventricular micromanometric pressure measurement and transesophageal Doppler echocardiograms. Within four or five beats after inferior vena caval balloon occlusion, left atrial loading was reduced as evidenced by a decrease in the slope of the left atrial v wave from 21 ± 4 to 13 ± 4 mm Hg/sec (p < 0.001) and by a decrease in the first crossover point of left atrial and left ventricular pressures from 5.6 ± 1.1 to 2.9 ± 1.5 mm Hg (p < 0.001). This decrease in left atrial loading resulted in reductions during early diastole of minimum left ventricular pressure (from 1.0 ± 0.8 to -0.4 ± 1.2 mm Hg, p < 0.001), the maximum early forward (i.e., left atrial pressure > left ventricular pressure) transmitral pressure gradient (from 2.8 ± 0.8 to 2.4 ± 0.5 mm Hg, p < 0.01); the slope of the rapid filling pressure wave (from 44 ± 11 to 38 ± 10 mm Hg/sec, p < 0.025); and the area of the reversed (i.e., left ventricular pressure > left atrial pressure) transmitral pressure gradient (from 79 ± 42 to 53 ± 33 mm Hg·msec, p < 0.05). During late diastole, both the heights and slopes of the left atrial and left ventricular A waves fell, resulting in a decrease in the maximum late transmitral pressure gradient (from 1.2 ± 0.7 to 0.9 ± 0.5 mm Hg, p < 0.05). Vena caval occlusion also altered Doppler transmitral velocity profiles during both the early and late phases of diastole. Peak velocity of the E wave decreased (from 50 ± 11 to 41 ± 7 cm/sec, p < 0.01) as did acceleration (from 880 ± 222 to 757 ± 258 cm/sec2, p < 0.025) and deceleration (from 597 ± 260 to 429 ± 197 cm/sec2, p < 0.025). Peak velocity of the A wave also fell (from 29 ± 9 to 22 ± 5 cm/sec, p < 0.005). Abrupt inferior vena caval occlusion did not significantly change heart rate or mean aortic pressure. Significant correlations were obtained between peak flow velocity during early diastole and the peak forward pressure gradient during early diastole (r = 0.67, p < 0.05), between peak flow velocity during late diastole and the peak pressure gradient during late diastole (r = 0.80, p < 0.01), and between deceleration rate of the Doppler E wave and the magnitude of the reversed transmitral pressure gradient (r = 0.60, p < 0.01). These results indicate that an acute reduction in left atrial loading conditions significantly alters the diastolic transmitral pressure relation and thus profoundly affects the Doppler flow velocity profile.