This study aims to investigate the uptake of the experimental ultrasmall superparamagnetic particles of iron oxide (USPIO) contrast agent DDM43/34 (Schering AG, Berlin, Germany) by aortic atherosclerotic plaques using magnetic resonance imaging (MRI) at 3 T. Six Watanabe heritable hyperlipidemic rabbits were injected with USPIO at doses of 0.1-1.0 mmol/kg Fe. Parasagittal magnetic resonance angiography (MRA) scans were acquired using 3D gradient-echo sequences before and after USPIO administration, then again after 6 h, 1 day, 2 days and 5 days. At later time points, when the USPIO concentration was too low to enhance blood signal, additional MRA scans were acquired during the infusion of gadopentate dimeglumine (Magnevist; Schering AG). In the images, widespread susceptibility artifacts demonstrated readily detectable USPIO uptake in the liver, bone marrow and lymphatic vessels. Surprisingly, however, no such effects could be associated specifically with the aortic vessel wall, in contrast to previous studies that showed strong uptake with similar pulse sequences. Histological analysis was performed on aortic slices from two animals, demonstrating that aortic plaques were active but showed very little USPIO uptake, consistent with MRI findings. We conclude that, despite the exciting potential of plaque detection using USPIO, some caution is advised since the absence of susceptibility effects does not necessarily imply the absence of plaque, even at 3 T, which offers increased sensitivity to susceptibility. Future work will investigate the dependence of such results on stage of plaque development, magnetic field strength and choice of contrast agent.