Hepatocellular carcinoma (HCC) remains one of the most important malignancies in Japan (1, 2). Lactic dehydrogenase (LDH), which is a glycolyticenzyme, and exists in various types of human tissue and neoplasms, has also been reported to demonstrate a high level (especially LDH 5) in the serum of patients with HCC (3-10). We herein report the findings of a 68-year-old male patient with hepatocellular carcinoma (HCC), whose serum lactic dehydrogenase (LDH) level more closely correlated with the clinical course than the alpha-feto-protein level (AFP). Both the AFP and LDH levels were high before the operation (AFP 1402 ng/ml; LDH 638 IU/L) (LDH1 11%; LDH2 24%; LDH3 34%; LDH4 19%; LDH5 12%). The levels of the serum LDH and AFP one week after the right hepatic lobectomy both decreased to 423 IU/L and 331 ng/ml, respectively. In addition, the LDH isozyme pattern returned to normal. Six weeks after the operation, the serum LDH increased to 3504 IU/L, however, the AFP levels remained low at 43.4 ng/ml, and the CT findings demonstrated multiple recurrent nodules in the whole remnant liver. At eighty-one days after the operation, the patient died due to a rupture of the recurrent HCC. Immunohistochemical observations were performed using the peroxidase labeled streptavidin-biotin technique with slight modifications and using two monoclonal antibodies for AFP and for Ki-67. Most portions of the primary tumor consisted of poorly to undifferentiated HCC. The portion of undifferentiated HCC did not stain for AFP antibody, but the portion of poorly differentiated HCC stained positively for it. It was thus speculated that LDH was mainly produced in the portion of undifferentiated HCC. In addition the undifferentiated HCC were strongly positive for Ki-67, while, in contrast, the poorly HCC was only weakly positive for Ki-67. Based on the above findings, HCC with a high serum level of LDH appears to show both a rapid growth and highly malignant tumors.