['Native tissue second harmonic imaging (SHI) implemented in two-dimensional (2D) echocardiography was found to improve left ventricular (LV) endocardial border delineation. Dobutamine stress echocardiography (DSE) depends on the ability to adequately visualize these borders. We analysed whether SHI, compared to fundamental imaging (FI), can improve echogenicity qualitatively and quantitatively, as well as looking at the diagnostic accuracy of the stress test.', 'Fifty consecutive patients with suspected or known coronary artery disease (history of myocardial infarction and/or coronary artery bypass grafting) underwent DSE sequentially by SHI as well as FI 3 days before or after quantitative coronary angiography. Regional mean echogenicity scores (0=uninterpretable; 4=excellent imaging) for SHI and FI at peak dobutamine titration were 1.8 +/- 0.8 and 1.0 +/- 0.6 (P=0.0020) for the anterior region, 2.3 +/- 0.8 and 1.5 +/- 0.7 (P=0.0002) laterally, 2.7 +/- 1.0 and 1.9 +/- 0.8 (P=0.0001) posteriorly, 2.9 +/- 0.8 and 2.2 +/- 0.7 (P<0.0006) inferiorly, 3.0 +/-0.7 and 2.2 +/- 0.7 (P=0.0001) septally, and 3.1 +/- 1.0 and 2.1 +/-0.8 (P=0.0001) anteroseptally, respectively. Medians [upper; lower quartiles] of a global endocardial visualization index (calculated analogously with the wall motion score index based on a 16-segment model recommended by the American Society of Echocardiography) for the harmonic and the fundamental techniques were 2.59 [2.91; 2.22] and 1.87 [2.19; 1.53] (P=0.0001) at rest, 2.62 [2.94; 2.13] and 1.84 [2.19; 1.50] (P=0.0001) at low dose dobutamine, 2.51 [3.00; 2.13] and 1.74 [2.00; 1.44] (P=0.0001) at peak dose dobutamine, and 2.52 [2.94; 2.19] and 1.76 [2.19; 1.38] (P=0.0001) at recovery, respectively. For repeated quantitative LV volumetry in the harmonic and fundamental modality by the same observer, coefficients of variation were 4.4 +/- 0.4 vs. 6.0 +/- 0.5 (P<0.0001) for end-diastolic volume, 7.4 +/- 0.8 vs. 9.2 +/- 1.1 (P<0.0001) for end-systolic volume, and 5.2 +/- 1.1 vs. 8.2 +/- 1.3 (P<0.0001) for ejection fraction, respectively. Sensitivity and specificity related to coronary angiography for both methods were 80% and 60% as well as 90% and 93%, respectively.'] Does native tissue second harmonic imaging improve endocardial and epicardial border definition in dobutamine stress echocardiography?