Echocardiographic evaluation of left ventricular (LV) systolic function relies on endocardial visualization, which can be improved when necessary using contrast enhancement. However, there is no method to automatically detect the endocardial boundary from contrast-enhanced images. We hypothesized that this could be achieved using harmonic power Doppler imaging. Twenty-two patients were studied in two protocols: (1) 11 patients with poorly visualized endocardium (> 3 contiguous segments not visualized) and (2) 11 consecutive patients referred for dobutamine stress echocardiography who were studied at rest and at peak dobutamine infusion. Patients were imaged in the apical four-chamber view using harmonic power Doppler mode (HP SONOS 5500) during LV contrast enhancement (Optison or Definity DMP115). Digital images were analyzed using custom software designed to automatically extract the endocardial boundary from power Doppler color overlays. LV cavity area was automatically measured frame-by-frame throughout the cardiac cycle, and fractional area change calculated and compared with those obtained by manually tracing the endocardial boundary in end-systolic and end-diastolic gray scale images. Successful border detection and tracking throughout the cardiac cycle was possible in 9 of 11 patients with poor endocardial definition and in 10 of 11 unselected patients undergoing dobutamine stress testing. Fractional area change obtained from power Doppler images correlated well with manually traced area changes (r = 0.82 and r = 0.97, in protocols 1 and 2, respectively). Harmonic power Doppler imaging with contrast may provide a simple method for semi-automated border detection and thus facilitate the objective evaluation of LV function both at rest and under conditions of stress testing. This methodology may prove to be particularly useful in patients with poorly visualized endocardium.