We have previously shown that human metallopanstimulin-1 (MPS-1) is a ubiquitous 9.4-kd multifunctional ribosomal S27/nuclear "zinc finger" protein that is expressed at high levels in a wide variety of actively proliferating cells and tumor tissues. In this study, we examined the expression of MPS-1 in chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Tissue samples were obtained at the time of tumor resection, needle biopsy, or liver transplantation. MPS- 1 was studied by immunohistochemistry by use of specific antibodies to the N-terminus of MPS-1 in a biotin/streptavidin-amplified system. In chronic hepatitis, hepatocytes had very weak MPS-1 immunostaining. In contrast, hepatocytes in regenerating cirrhotic nodules stained strongly for MPS-1. In well-differentiated hepatocellular carcinoma, MPS-1 presence was intense at the periphery of the malignant nodule. In poorly differentiated hepatocellular carcinoma, MPS-1 presence was notably intense in malignant hepatocytes invading the septal tissues, in close contact with neovascular structures. These results suggest that MPS-1 may be involved in both progression toward malignancy in regenerating cirrhotic nodules and in subsequent steps of hepatocarcinogenesis.