Superparamagnetic iron oxide (AMI-25), a reticuloendothelial cell-specific contrast agent for magnetic resonance (MR) imaging, was evaluated for its ability to permit detection of splenic metastases in 18 patients. Superparamagnetic iron oxide, at a dose of 30 mumol of iron per kilogram, decreased the signal intensity of spleen from 19.5 +/- 4.8 to 3.1 +/- 2.2 (spin-echo sequence, repetition time msec/echo time msec = 1,500/42; P less than .05), without changing the signal intensity of tumor. As a result, the tumor-spleen contrast-to-noise ratio increased from 0.2 (tumor isointense relative to spleen) to 18.0 (tumor hyperintense relative to spleen). As a consequence of increased contrast, splenic tumors were detected in four of 18 patients (45 individual lesions; P less than .05), whereas nonenhanced MR imaging permitted detection of splenic lesions in only two of 18 patients (four individual lesions). Maximum tumor-spleen contrast was achieved within 60 minutes after intravenous administration. These initial clinical results indicate that MR imaging with superparamagnetic iron oxide may offer improved accuracy in the diagnosis of splenic tumors.