The purpose of our study was to evaluate the ability of superparamagnetic iron oxide (SPIO)-enhanced MR imaging to detect liver fibrosis in patients with chronic liver disease and to compare the findings with histopathological data. Sixty-seven patients with chronic hepatitis ( n=58) or focal nodular hyperplasia (FNH; n=9) were studied using a 1.5-T MR system. The protocol included proton density-weighted, T2-weighted spin-echo (SE) and fast SE (FSE) sequences before and after SPIO administration and T2*-weighted gradient-recalled-echo (GRE) sequences after SPIO. Pre- and post-contrast T2-weighted and T2*-weighted sequences were retrospectively evaluated by three independent observers for evidence of non-tumor hypersignal intensities. Three liver patterns were considered: thick reticulations; thin reticulations; and/or multiple areas of hypersignal intensities. Unenhanced or enhanced patterns were compared with histopathological specimens, which had been obtained by percutaneous biopsy of the right lobe within a maximum of 12 months of MR examination. Liver fibrosis was histologically graded using a five-level scale (F0-F4), according to the METAVIR classification. Histopathology demonstrated significant fibrosis (F2-F4) in 57 patients, non-significant fibrosis in 1 patient (F1), and normal liver surrounding FNH in 9 patients (F0). After SPIO administration, at least one pattern of non-tumor hypersignal intensities was seen in 43 (76%) of the 57 patients with F>/=2 with good agreement (kappa=0.68) compared with 2 (20%) of the 10 F0/1 patients ( p<0.01). Attenuated non-homogeneous liver-signal intensities with persistent thick reticulations, thin reticulations, or multiple areas of hypersignals were observed in, respectively, 30, 52, and 56% of patients with F>/=2 with moderate agreement (kappa=0.51). Before SPIO, MR images were positive in 21 of 57 (37%) F>/=2 and zero F0/1 patients. Post-contrast proton-density-weighted and T2*-weighted GRE were the most sensitive sequences for detecting non-tumor hypersignal intensities. In patients with chronic liver diseases, SPIO-enhanced MR imaging exhibits non-tumor hypersignal intensities indicative of liver fibrosis by decreasing the signal from the non-fibrotic areas where Kupffer cells are present.