The MAGE-1 gene, originally isolated from a human melanoma cell line, directs the expression of a potential tumor-rejection antigen, MZ2-E. This antigen is recognized by autologous cytotoxic T lymphocytes in association with a major histocompatibility complex class I molecule (HLA-A1), and has provided a basis for specific immunotherapy for melanoma patients. Here we show a high frequency of expression of the MAGE-1 gene in hepatocellular carcinoma (HCC). We examined the expression of the MAGE-1 gene in cell lines originated from hepatoma cells and in tumor and nontumor tissues of livers with HCC by reverse-transcription polymerase chain reaction (RT-PCR) and subsequent Southern blotting. MAGE-1 messenger RNA (mRNA) was expressed in three of four HCC cell lines (75%) and in 16 of 20 (80%) resected HCCs though none was detected in nontumor tissues. The high frequency expression of MAGE-1 gene in HCCs suggests the possibility as a target for tumor- specific immunotherapy for HCC patients.