Since hepatocellular carcinoma (HCC) is frequently presented at an advanced stage, only a small portion of patients with HCC can be treated with local modalities. Gene therapy is, therefore, one of the more promising approaches for patients with advanced HCC. To develop a new strategy for targeting gene delivery to the hepatic tumor, the efficiency of the transarterial delivery of liposome-DNA complex was evaluated in VX2 carcinoma implanted into the liver of rabbits. A mixture of pSV-beta galactosidase plasmid (40 micrograms), lipofectin (80 microliters), and transferrin (852 micrograms), the optimal proportion of which determined in vitro, was infused via the hepatic artery of a rabbit with VX2 hepatic tumors. The efficiency of trans-arterial gene delivery was compared to that of intra-tumoral injection. Rabbits (5 in each group) were sacrificed 48 hours after gene delivery and hepatic tissues were examined using X-gal staining. beta-galactosidase staining was observed exclusively within the tumor following the trans-arterial gene transfer. In contrast, adjacent peritumoral cells in addition to hepatic tumor cells were transfected by the intra-tumoral injection of transgene. These data indicate that enhanced gene expression in hepatic tumors is possible using trans-arterial delivery of the liposome-DNA complex.