In this study, norcantharidin was compared with adriamycin and mitomycin C for its inhibitory action in the growth of cultured human hepatocellular carcinoma HepG2 cells. The IC50 of adriamycin and mitomycin C on HepG2 cells was 7.3 microM and 27 microM, respectively, whereas the IC50 of norcantharidin for inhibiting the growth of HepG2 cells was as high as 1900 microM. After HepG2 tumor-bearing nude mice were treated with 12 daily intraperitoneal injections of norcantharidin (2 mg/kg), the increase in tumor size was significantly slower than that of untreated controls. The mean survival time of untreated tumor-bearing nude mice was 129 days, whereas in the tumor-bearing nude mice treated with norcantharidin, the mean survival time was significantly prolonged to 194 days (P < 0.0001). It is concluded that norcantharidin may have a potential role in the treatment of human hepatocellular carcinoma.