Superparamagnetic iron oxide (AMI 25) is a promising new contrast agent for imaging the reticuloendothelial-system. Iron oxide crystals possess a large magnetic susceptibility and enhance proton relaxation rates, especially transverse relaxation (T2). In order to guide the clinical utilization of this contrast media we analyzed 4 patients with malignant lesions of the liver before and after slow intravenous administration (20 mumol Fe/kg) of AMI 25. We performed two magnetic resonance (MR) sequences at different times using a 0.35 T magnet. MR signal-to-noise ratio (SNR) of the reticuloendothelial system (particularly the liver SNR) decrease promptly. The maximum decrease in SNR (67-72% for the liver, 46-65% for the spleen, 23-41% for the bone marrow) is observed 3 h after injection (P less than 0.01). However, except the peak of contrast enhancement in T1-weighted sequences of splenic tissue, the curve describes a plateau within 30 min and 6 h, allowing a delay between injection and imaging. T2-weighted sequences give a greater contrast-to-noise ratio (CNR) by adding the spontaneous tumor contrast to the effect yielded by AMI 25. These results suggest that images must be acquired between 1 and 6 h after intravenous administration of superparamagnetic iron oxide.