The effects of the combination of genistein, a tyrosine kinase inhibitor, and adriamycin, an anthracycline anticancer drug, were studied in three human breast carcinoma cell lines (MCF-7/WT, MCF-7/ADR(R) and MDA-231) differing in estrogen receptor status and adriamycin sensitivity. Genistein inhibited cell proliferation in all three cell lines (IC50 between 7.0 and 37.0 microM). The combination produced additive to synergistic effects; epidermal growth factor receptor modulation by adriamycin does not seem to be involved in this interaction. The possible therapeutic advantage of this drug combination, especially on hormone-independent and multidrug resistant tumor cells, deserves further investigation.