Improved echocardiographic endocardial border delineation aids in the assessment of ventricular function and wall motion abnormalities. Microbubble-based contrast agents provide excellent echogenicity but a short-lived effect as microbubbles are susceptible to destruction by ultrasound and are rapidly eliminated by the lungs. In contrast, liquid perfluorocarbon (PFC) nanoparticles exhibit long circulatory times and are stable to insonification but have poor echogenicity. Ideally, a contrast agent should demonstrate long circulatory persistence, resistance to ultrasonic destruction, while displaying significant echogenicity. This study demonstrates the effectiveness of biocompatible, liquid PFC nanoparticles as a blood pool contrast agent. When imaged with Power Doppler Harmonic Imaging (PDHI), this agent exhibited marked blood pool enhancement lasting over 1 hour. Furthermore, the contrast enhancement was achieved at doses of 0.7% blood volume; a dose far smaller than had been previously published in studies utilizing liquid PFC nanoparticles with conventional imaging. In order to investigate the influence of particle size on blood pool contrast effect, liquid PFC nanoparticles were formulated with diameters of 232 and 465 nm. The nanoparticles were then administered to canines (N = 10), with 7 canines receiving the 232 nm nanoparticles and the remainder receiving the 465 nm nanoparticles at a dose of 0.5 ml/kg. PDHI revealed marked blood pool enhancement in all three canines receiving the 465 nm nanoparticles but minimal contrast effect in the canines receiving the 232 nm nanoparticles. This data suggests that PFC nanoparticles in conjunction with PDHI may serve as an important adjunct for the assessment of ventricular function and wall motion abnormalities. This study provides the first documented report of liquid PFC nanoparticles utilized as blood pool contrast agents with PDHI.