Polypeptides in bee venom (PBV) produced a significant growth inhibition against SMMC-7721 human hepatoma cell line. Analysis of the mechanisms of cell death indicated that PBV induced an apoptotic cell death. SMMC-7721 cells exposed to PBV (10.0 microg mL(-1)) produced an insignificant morphological change. Analysis of the cytotoxicity with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay confirmed that the cytotoxic effects of PBV were dose- and timedependent. The result of Ki67 immunohistochemistry demonstrated that the proliferation of SMMC-7721 cells treated with PBV (10.0 mug mL(-1)) was inhibited. The apoptotic cell death was then confirmed by annexin V, propidium iodide staining and DNA fragmentation analysis. In in-vivo experiments, treatment with PBV (1.5 or 3 mg kg(-1)) resulted in a significant retardation of SMMC-7721 cell growth in Balb/c nude mice. These findings suggested that PBV could be used as a chemotherapeutic agent against tumours.