To improve ultrasound contrast agents targeted to the adhesion molecules P-selectin and VCAM-1 for the purpose of molecular imaging of atherosclerotic plaques, perfluorocarbon-filled phospholipid microbubble contrast agents were coupled by a polyethylene glycol-biotin-streptavidin bridge with mAb MVCAM.A(429), a sialyl Lewis x polymer (PAA-sLe x ), or both (dual). Approximately three hundred thousand antibody molecules were coupled to the surface of each microbubble. Recombinant mouse P-selectin and/or VCAM-1 coated on flow chambers showed saturation of binding at approximately 15 ng/μl, resulting in 800 and 1200 molecules/μm 2 for P-selectin and VCAM-1, respectively. Dual substrates coated with equal concentrations of P-selectin and VCAM-1 had site densities between 50 and 60% of single substrates. When microbubbles were perfused through flow chambers at 5×10 6 microbubbles/ml (wall shear stress from 1.5 to 6 dyn/cm 2 ) dual targeted microbubbles adhered almost twice as efficiently as single targeted microbubbles at 6 dyn/cm 2 . The present study suggests that dual targeted contrast agents may be useful for atherosclerotic plaque detection at physiologically relevant shear stresses.