Manganese (II) N,N'-dipyridoxylethylenediamine-N,N' diacetate 5,5'-bis(phosphate) (MnDPDP) is a hepatobiliary agent that is incorporated into the hepatocyte. We retrospectively reviewed our experience with 39 focal liver lesions in 20 patients studies with MnDPDP-enhanced hepatic magnetic resonance (MR) imaging to determine whether hepatocellular carcinoma (HCC) could be differentiated from tumors of nonhepatocyte origin (metastases, cavernous hemangiomas, etc.) For all cases, liver parenchyma enhanced significantly following MnDPDP administration. All HCCs (6) showed significant tumor enhancement resulting in decreased tumor conspicuity compared to precontrast images [average 37% decrease in tumor-liver contrast to noise ratio (C/N)]. In contradistinction, other focal liver lesions showed little or no tumor enhancement resulting in increased lesion conspicuity (average 100% increase in tumor-liver C/N ratio). Our preliminary data suggest that MnDPDP-enhanced MR images may enable differentiation of HCC from other focal liver masses of nonhepatocyte origin.