Our study was designed to compare the utility of fundamental and second harmonic imaging (SH) for visualization of the left ventricular (LV) endocardial border. SH is a new imaging modality using nonlinear acoustic response, which may provide better endocardial border delineation. Standard apical views were studied in 42 patients using fundamental frequency (FF), SH without contrast (1.6- to 1.8-MHz and 2.1- to 2.5-MHz transmission frequencies), and SH after an intravenous injection of 2.5 g of Levovist. The quality of endocardial delineation in 16 standard segments was scored from 0 to 2. The endocardial visualization index was calculated as a mean of the scores. SH with and without contrast significantly improved LV endocardial border detection (endocardial visualization index 1.25+/-0.53, 1.64+/-0.67, 1.55+/-0.69, and 1.73+/-0.28 for fundamental, lower, and higher frequency harmonic and contrast-harmonic mode, respectively, p <0.005). Improvement was found in all LV segments. The number of invisible segments decreased from 142 (FF) to 54, 112, and 61 (in lower, higher, and contrast SH mode, respectively, p <0.001). Endocardial delineation in the apical segments using SH was optimal after contrast injection. In the basal LV area, contrast-enhanced images were less informative because of signal attenuation. Thus, SH significantly improves visualization of the LV endocardial border. Contrast enhancement with Levovist improves imaging of the apical segments but has no additional advantage in the basal segments. SH emerges as first-line modality for studies of LV function.