Background: Tissue Doppler imaging (TDI) is a novel method of color- coding myocardial velocity on-line. The objective of the present study was to evaluate endocardial velocity with TDI as a method of objectively quantifying alterations in regional contractility over a wide range induced by inotropic modulation. Methods and Results: Myocardial length crystals were used to simultaneously assess regional left ventricular (LV) function, and high- fidelity pressure and conductance catheters were used to assess global LV contractility by pressure-volume relations in nine open-chest dogs. Mid-LV M- mode and two-dimensional color TDI images were recorded during control and inotropic modulation stages with dobutamine and esmolol. Predicted significant increases in TDI indices occurred with dobutamine: peak systolic velocity of 4.41±1.07 to 6.67±1.07 cm/s*, systolic time-velocity integral (TVI) of 0.43±0.12 to 0.62±0.10 cm*, and diastolic TVI of 0.49±0.11 to 0.71±0.17 cm*. Opposing significant decreases occurred with esmolol: peak systolic velocity of 4.46±0.94 to 2.31±0.81 cm/s*, systolic TVI of 0.47±0.12 to 0.19±0.11 cm*, and diastolic TVI of 0.55±0.11 to 0.33±0.11 cm* (*all P<.001 versus control). Changes in TDI peak systolic velocity were correlated with changes in fractional shortening (r=.88) and shortening velocity (r=.87) by sonomicrometry. Changes in TDI peak velocity from multiple mid-LV sites also correlated significantly with maximal elastance (r=.85±.04) from pressure-volume relations. Conclusions: TDI measures reflect directional and incremental alterations in regional and global LV contractility and have the potential to quantify regional LV function.