The changes in the plasma level of PIVKA-II (Protein Induced by Vitamin K Absence or Antagonist-II) following the treatment or progress of the disease was studied in 60 patients with hepatocellular carcinoma. The positivity rate determined by the changes in PIVKA-II was 58.4 percent (35/60 cases) and was about the same as those reported so far, all of which were obtained by a single determination of PIVKA-II. Plasma PIVKA-II was elevated in 61.9 percent (13/21 cases) of alpha-fetoprotein negative patients and it was almost identical with the overall positivity rate. In parallel with serum alpha-fetoprotein, the plasma level of PIVKA-II was decreased after the surgery or transcatheter arterial embolization and was increased when the recurrence or progress of the disease was observed. Furthermore, the nonspecific elevation of PIVKA-II due to the associated liver cirrhosis or chronic hepatitis was infrequent compared with that of alpha-fetoprotein. In 18 cases positive with both PIVKA-II and alpha-fetoprotein, a close correlation (R = 0.91) was observed between the changes of these markers during the progress or treatment of the disease. Thus, it was suggested that determination of PIVKA-II in blood might be useful not only in the diagnosis but in monitoring the progress or the effectiveness of treatments in hepatocellular carcinoma.