Two-dimensional echocardiography is used routinely and reliably to assess regional and global left ventricular (LV) function. A prerequisite for this assessment is the determination of LV wall thickening as defined by endocardial border motion. Enhancement of endocardial border definition (EBD) by contrast agents has been demonstrated both at rest(1) and during stress,(2,3) especially with the second-generation agents containing perfluorocarbon gases.(4,5) Contrast agents for enhancement of EBD have yet to gain widespread use in clinical practice. A variety of safe transpulmonary ultrasonic contrast agents(6-8) have been developed, driven in part by the desire to assess myocardial perfusion by contrast echocardiography,(9) and 2 such agents (Albunex and Optison [formerly FS-069, Molecular Biosystems Inc., San Diego, California]) have been approved for clinical use in the US. Recent advances in ultrasound technology have paralleled the advent of contrast agents. A major development has been harmonic imaging.(10,11) This technology improves the sensitivity of ultrasound for detection of contrast microbubbles by producing images from signals received at twice the applied (fundamental) frequency. The harmonic signals generated by microbubbles are far stronger than those of the surrounding tissues.(12,13) This study aimed to assess the improvement in EBD provided by harmonic imaging of a commercially available second-generation contrast agent.