Abstract: We have compared in vitro binding of adriamycin(ADR) and amsacrine(AMSA)with DNA, the toxicity, and the antitumor activity of ADR-DNA and AMSA-DNA, after in-traperitoneal(ip) injection in mice. The binding of ADR with DNA is 100--fold higher than that ofAMSA with DNA. The overall toxicity of ADR--DNA is singnificantly lower than that of ADR.ADR--DNA is more effective than ADR against three models of S180 sarcoma (by sc,ip and iv inocu-lation into mice). The peak levels of ADR--DNA and ADR were 265±24 ng·ml^-1 versus 108±16ng·ml^-1(P<0. 01). AUC 0～12 h were 1064±84 ng·h^-1 ·ml^-1 versus 382±27 ng·h^-1·ml^-1 (P<0. 01). The levels of ADR in most of tissues and tumor after adminstration of ADR--DNAwere higher than those after administration of ADR. Moreover, there is no difference in toxicity,therapeutic effects as well as AUC between AMSA--DNA and AMSA.