The effect of cepharanthine on the cytotoxicity of doxorubicin (DOX) in p388 leukemia cells was studied in vitro and in vivo. Nontoxic levels of cepharanthine enhanced the sensitivity to doxorubicin in p388 cells in vitro. The potentiation of antitumor activity of DOX by cepharanthine against mice bearing p388 cells was also observed.