Des-y-carboxy prothrombin [DCP], a protein induced by vitamin K absence or antagonist-I1 and also abbreviated PIVKA-11, was evaluated as a serologic marker for hepatocellular carcinoma (HCC). Its plasma levels were measured by enzyme immunoassay (E-1023) using an anti-DCP monoclonal antibody in 514 patients with various diseases. Of 120 patients with HCC, 76 (63%) had abnormal DCP levels greater than 0.1 arbitrary unit (AU)/ml and 58 (48%) showed levels greater than 0.3 AU/ml. When a diagnostic minimum level of 0.3 AU/ml was applied for DCP, false-positive cases of HCC were virtually eliminated. In some patients with HCC, plasma DCP levels normalized after surgical resection of the tumor. However, they rose again later with recurrence of the disease. The sensitivity of DCP in the diagnosis and monitoring of HCC was increased by serial and simultaneous determinations of alpha-fetoprotein (AFP), because high DCP levels were observed more often in low AFP-producing HCC patients. Elevated plasma DCP 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 DCP levels. These results suggested strongly that DCP was synthesized by the hepatoma cells.