The aim of this prospective study was to obtain the first human safety and magnetic resonance (MR) imaging results with a new formulation of superparamagnetic iron oxide (SPIO) (SHU 555 A). The SPIO was tested at four iron doses, from 5 to 40 mumol/kg. Laboratory tests and clinical measurements were done in 32 healthy volunteers for up to 3 weeks after administration. MR imaging at 1.5 T was performed before and 8 hours to 14 days after fast intravenous injection (500 mumol Fe/min) of the SPIO (six subjects per dose). Results of this phase I study demonstrate that SHU 555 A at a concentration of 0.5 mol Fe/L was well tolerated. A dose-dependent minor increase in activated partial thromboplastin time, which remained within the normal range, was seen. All doses of SPIO caused a signal loss in both liver and spleen (P < .05) with a spin-echo sequence (TR = 2,300 msec, TE = 45 msec). The signal losses in the liver 8 hours after contrast agent injection were 58%, 79%, 82%, and 87% for the 5, 10, 20, and 40 mumol Fe/kg doses, respectively. The corresponding signal losses in the spleen were 23%, 45%, 65%, and 78%, respectively. The doses that reduced signal intensity by half were 3.1 mumol Fe/kg for the liver and 12.8 mumol Fe/kg for the spleen. The results suggest that the new SPIO formulation is a safe and efficient MR contrast agent.