Plasma abnormal prothrombin (protein induced by vitamin K absence or antagonist-II: PIVKA-II) was evaluated as a serological marker for hepatocellular carcinoma (HCC). Its plasma levels were measured by enzyme immunoassay using an anti-PIVKA-II monoclonal antibody in 1010 patients with various diseases. Of 192 patients with HCC, 116 (60%) had abnormal PIVKA-II levels greater than 0.1 AU/ml. Elevation of PIVAK-II levels was observed rarely in chronic hepatitis, liver cirrhosis and other malignant tumors. Plasma PIVKA-II levels in HCC increased with tumor size. Normal levels were observed in patients with tumors measuring 2 cm or less in diameter. As a result, diagnostic application of plasma PIVKA-II levels to small liver tumors is limited. The sensitivity of PIVKA-II in the diagnosis and monitoring of HCC was increased by serial and simultaneous determinations of AFP, because high PIVKA-II levels were observed more often in low AFP-producing HCC patients. In some patients with HCC, plasma PIVKA-II levels decreased after surgical resection of the tumor or chemoembolization with cisplatin suspended in Lipiodol (LPS), but later rose again with recurrence of the disease. Elevated plasma PIVKA-II levels were not related to low vitamin K concentration in the serum. In fact, in many patients vitamin K administration resulted in only a moderate reduction of PIVKA-II levels. From these results, plasma PIVKA-II assay by the EIA method using a monoclonal antibody is a useful tool for the diagnosis and monitoring of HCC, particularly in HCC patients with low AFP levels.