There is a need for better methods to quantify regional myocardial function. In the present study, we investigated the feasibility of quantifying regional function in terms of a segmental myocardial work index as derived from strain Doppler echocardiography (SDE) and invasive pressure. In 10 anesthetized dogs, we measured left ventricular (LV) pressure by micromanometer and myocardial longitudinal strains by SDE and sonomicrometry. The regional myocardial work index (RMWI) was calculated as the area of the pressure-strain loop. As a reference method for strain, we used sonomicrometry. By convention, the loop area was assigned a positive sign when the pressure-strain coordinates rotated counterclockwise. Measurements were done at baseline and during volume loading and left anterior descending coronary artery (LAD) occlusion, respectively. There was a good correlation between RMWI calculated from strain by SDE and strain by sonomicrometry ( y = 0.73 x + 0.21, r = 0.82, P < 0.01). Volume loading caused an increase in RMWI from 1.3 ± 0.2 to 2.2 ± 0.1 kJ/m3 ( P < 0.05) by SDE and from 1.5 ± 0.3 to 2.7 ± 0.3 kJ/m3 ( P = 0.066) by sonomicrometry. Short-term ischemia (1 min) caused a decrease in RMWI from 1.3 ± 0.2 to 0.3 ± 0.04 kJ/m3 ( P < 0.05) and from 1.3 ± 0.3 to 0.5 ± 0.2 kJ/m3 ( P < 0.05) by SDE and sonomicrometry, respectively. In the nonischemic ventricle and during short-term ischemia, the pressure-strain loops rotated counterclockwise, consistent with actively contracting segments. Long-term ischemia (3 h), however, caused the pressure-strain loop to rotate clockwise, consistent with entirely passive segments, and the loop areas became negative, −0.2 ± 0.1 and −0.1 ± 0.03 kJ/m3 ( P < 0.05) by SDE and sonomicrometry, respectively. A RMWI can be estimated by SDE in combination with LV pressure. Furthermore, the orientation of the loop can be used to assess whether the segment is active or passive.