PURPOSE: To evaluate the clinical and biologic safety of ultrasmall superparamagnetic iron oxide particles (AMI-227) as a contrast agent for magnetic resonance (MR) lymphography and to assess their efficacy for the differentiation of metastatic and benign nodes in patients with urologic and pelvic cancer. MATERIALS AND METHODS: Thirty adults suspected of having lymph node metastases underwent MR imaging before and 22-26 hours after intravenous infusion of AMI-227 (1.7 mg Fe/kg). Sixty histopathologically proved lymph nodes were analyzed on MR images, and 29 of these nodes were also analyzed quantitatively. RESULTS: AMI-227 was well tolerated with no major side effects. It allowed the detection of 10 additional nodes relative to those detected at MR imaging without AMI-227. None of the 27 metastatic nodes showed a decrease in signal intensity (SI) on AMI-227-enhanced images; nine of 27 metastatic nodes showed an increase in SI on T1-weighted images, probably resulting from altered capillary permeability in the tumor. A visually perceptible reduction in SI, indicating active AMI-227 uptake, was observed on postcontrast T2- and T2*-weighted images in 16 of 21 benign nodes. The SI ratio of benign nodes was lower than that of metastatic nodes on T2- and T2*-weighted images. The sensitivity of AMI-227-enhanced MR lymphography was 100%, and the specificity was 80%. CONCLUSION: AMI-227 is safe and may facilitate the differentiation of metastatic and benign nodes in patients with urologic and pelvic cancers.