We assessed the combined antitumor activity of docetaxel and doxorubicin (DXR) and tetrahydropyranyl-adriamycin (THP) using the human breast carcinoma cell lines R-27 and MDA-MB-231. Synergistic antitumor activity was observed for both combined docetaxel and DXR, and docetaxel and THP against R-27 cells when contacted simultaneously. However, only additive effects were observed against MDA-MB-231 cells. Intracellular concentrations of DXR and THP in R-27 cells were significantly increased by docetaxel pretreatment, however, this increase was not observed in MDA-MB-231 cells, which exhibited only additive sensitivity to the treatment. Thus, docetaxel increased the antitumor activity of anthracyclines by increasing their intracellular concentrations.