Superparamagnetic iron oxide (SPIO) particles are a potent new class of MR contrast agents affording improved detection of hepatic and splenic neoplasms. In this report we review the development of this agent through preclinical studies and early clinical results at Massachusetts General Hospital during a 5-year investigation. SPIO particles are sequestered by normal phagocytic Kupffer cells of the reticuloendothelial system (RES) but are not retained in tumor tissue. Consequently, there is a fivefold increase in T2 relaxation between normal RES tissue and tumor, with a comparable advantage in quantitative signal-to-noise ratio, contrast-to-noise ratio, and lesion detectability in the liver and spleen on MR imaging. Increased lesion conspicuity can be exploited to decrease threshold size for lesion detection to less than 3 mm. Clinically beneficial effects occur with a variety of mildly T2-weighted spin-echo pulse sequences; gradient-echo techniques show even greater benefit after administration of SPIO. Metabolically, pharmaceutical-grade preparations are biodegradable and bioavailable, being rapidly turned over into body iron stores and incorporated into erythrocyte hemoglobin. Early dose-escalation clinical trials have identified a probable clinical dose range of 10-20 mumols Fe/kg body weight. In the United States, SPIO compounds evaluated to date are still approved for use in investigational studies only. Newer commercial formulations currently being evaluated may extend clinical safety margins.