Adrimycin and cisplatin have been known to be effective in osteosarcoma respectively and many clinical reports showed that the combination of adriamycin and cisplatin had good therapeutic results. It is virtually impossible to assess the cytotoxic effect of anticancer agent quantitatively in vivo. The demonstration of true supra-additive tumor cell kill would imply interaction of the two cytotoxic agents at cellular level and would have profound implications for biochemical studies. In order to study the interaction of adriamycin and cisplatin at a cellular level, we conducted an in vitro tetrazolium-based colorimetric assay for cytotoxicity(MTT assay) and an isobologram analysis to test combinations of the two drugs on 5 human osteosarcoma cell lines. Using an accurate test for in vitro synergy, we obtained the following results. 1. The combination of adriamycin and cisplatin demonstrated a synergic cytotoxic effect on SNU-47 and SaOS-2 cell lines. 2. The combination of adriamycin and cisplatin did not demonstrate synergic cytotoxic effect on U-2-0S and MG-63 cell lines. 3. We could not obtain the constant result on G-292 cell line. 4. MTT assay and isobologram analysis were very useful to document the interaction of the anticancer agents quantitatively at cellular level in vitro. In conclusion, the combination of adriamycin and cisplatin demonstrated synergistic cytotoxic effects on some cell lines and did not on other cell lines. This study have implication for the selection of new synergic combination regimens and we hope it would be possible to select the appropriate therapeutic regimen for the patient individually with the advancement of in vivo study.